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Volume 270, Number 48, Issue of December 1, 1995 pp. 28495-28498 ©1995 by The American Society for Biochemistry and Molecular Biology, Inc.

Protein Kinase C: Structure, Function, and Regulation (*) Alexandra C. Newton

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From the Department of Pharmacology, University of California at San Diego, La Jolla, California 92093-0640 INTRODUCTION Structure Function Regulation Pseudosubstrate Regulation Regulation by Phosphorylation in Vivo Conclusion FOOTNOTES ACKNOWLEDGEMENTS REFERENCES

INTRODUCTION The protein kinase C family of enzymes transduces the myriad of signals promoting lipid hydrolysis. The prevalence of this enzyme family in signaling is exemplified by the diverse transduction mechanisms that result in the generation of protein kinase C's activator, diacylglycerol. Signals that stimulate members of the large families of G protein-coupled receptors, tyrosine kinase receptors, or non-receptor tyrosine kinases can cause diacylglycerol production, either rapidly by activation of specific phospholipase Cs or more slowly by activation of phospholipase D to yield phosphatidic acid and then diacylglycerol(1, 2, 3) . In addition, fatty acid generation by phospholipase A2 activation modulates protein kinase C activity(3) . Thus, multiple receptor pathways feeding into multiple lipid pathways have the common end result of activating protein kinase C by production of its second messenger. Phorbol esters, potent tumor promoters, can substitute for diacylglycerol in activating protein kinase C

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(1, 2, 3) . Unlike diacylglycerol, phorbol esters are not readily metabolized, and treatment of cells with these molecules results in prolonged activation of protein kinase C. As a result, phorbol esters have proved invaluable in dissecting out protein kinase C-catalyzed phosphorylations in vivo. In addition to regulation by diacylglycerol or phorbol esters, all isozymes of protein kinase C require phosphatidylserine, an acidic lipid located exclusively on the cytoplasmic face of membranes, and some isozymes require Ca for optimal activity (4, 5, 6, 7) . This review discusses the structure of the protein kinase C family, its enzymatic function, and how structure and function are regulated by 1) cofactors and 2) phosphorylation.

Structure Members of the protein kinase C family are a single polypeptide, comprised of an N-terminal regulatory region (approximately 20-40 kDa) and a C-terminal catalytic region (approximately 45 kDa) (Fig. 1). Cloning of the first isozymes in the mid-1980s revealed four conserved domains: C1-C4(8) . Each is a functional module, and many unrelated proteins have one or the other(9) . The function of each of these domains has been established by extensive biochemical and mutational analysis; the C1 domain contains a Cys-rich motif, duplicated in most isozymes, that forms the diacylglycerol/phorbol ester binding site (Fig. 1, orange) (7) ; this domain is immediately preceded by an autoinhibitory pseudosubstrate sequence (Fig. 1, green)(10) ; the C2 domain contains the recognition site for acidic lipids and, in some isozymes, the Ca -binding site (Fig. 1, yellow) (9) . The C3 and C4 domains form the ATP- and substrate-binding lobes of the kinase core (Fig. 1, pink and cyan)(11) . The regulatory and catalytic halves are separated by a hinge region that becomes proteolytically labile when the enzyme is membrane-bound(6) ; the proteolytically generated kinase domain (protein kinase M), freed of inhibition by the pseudosubstrate, is constitutively active (12) .

Figure 1: Schematic representation of the primary structure of conventional, novel, and atypical protein kinase Cs. Indicated are the pseudosubstrate domain (green), C1 domain comprising one or two Cys-rich motifs (orange), C2 domain (yellow) in the regulatory half, and the ATP-binding lobe (C3, pink) and substrate-binding lobe (C4, teal blue) of the catalytic region. The C2 domain of novel protein kinase Cs lacks amino acids involved in binding calcium but has key conserved residues involved in maintaining the C2 fold (hence its description as ``C2-like''). Atypical protein kinase Cs have only one Cys-rich motif, and phorbol ester binding has not been detected.

To date, 11 protein kinase C isozymes have been identified and classified into three groups based on their structure and cofactor regulation(3) . The best characterized and first discovered are the conventional protein kinase Cs: , two alternatively spliced variants I and II, and . This class distinguishes itself from the others in that function is regulated by Ca ; its C2 domain contains a putative Ca -binding site (see below). The next well characterized are the novel protein kinase Cs: , , (L), , and µ. These isozymes are structurally similar to the conventional protein kinase Cs, except that the C2 domain, while maintaining structural residues, does not have the functional groups that appear to mediate Ca binding (see below). The least understood isozymes are the atypical protein kinase Cs: and (I). These differ significantly in structure from the other two classes; first, the C1 domain contains

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only one Cys-rich motif (not two), and second, key residues that maintain the C2 fold do not appear to be present. Furthermore, these isozymes have been reported not to respond to phorbol esters in vivo or in vitro(3) . Perhaps adding to the three groups, two kinases with a C2 domain similar to that of novel protein kinase Cs, but with no C1 domain, have been identified(13, 14) . The crystal structure of the second Cys-rich repeat from the C1 domain of protein kinase C was solved recently with (Fig. 2A) and without bound phorbol ester by Hurley and co-workers(15) , as was the NMR structure of the corresponding repeat from protein kinase C , in the absence of ligand(16) . Strikingly, this sheet-rich domain undergoes no conformational change upon ligand binding. Rather, binding of phorbol ester plugs the hydrophilic binding site (a groove formed by two unzipped strands), so that the top third of the domain displays a contiguous hydrophobic surface(15) .

Figure 2: Structures of protein kinase C's domains. A, C1 domain. The ribbon and surface diagram of amino acids 231-280 in the second Cysrich domain of protein kinase C with bound phorbol ester (green) based on the coordinates of Zhang et al.(15) is shown. Conserved Cys (yellow) and His (purple) that coordinate the two zinc atoms of each cysteine-rich repeat (78) (green balls) are indicated. The arrow indicates the C12 position of the phorbol ester that is fatty acylated in bioactive phorbol esters(51) . B, C2 domain. The ribbon diagram of residues 167-240 from the C2 domain of synaptotagmin based on the coordinates of Sutton et al. (17) is shown. The five aspartates in the Ca -binding site are indicated in pink, the bulky hydrophobics on the back face in purple, and the adjacent two strands that are positively charged and likely constitute the acidic lipid-binding surface are in blue. Residues shown in orange are conserved in all C2 domains(9) . C, catalytic (C3 and C4) domain. The modeled structure of residues 340-632 of protein kinase C II with bound pseudosubstrate (residues 928) (20) is shown. The upper lobe, involved primarily in nucleotide binding, is mainly sheet (pink) and the lower lobe, containing the substrate-binding cavity, is predominantly helix (teal blue). Indicated are ATP (cream), two Mn atoms (red dots), and the pseudosubstrate (green) with the orange dot representing the alanine at the phosphoacceptor position. The yellow loop at the entrance to the catalytic site (below ATP) is the activation loop(11) ; phosphorylation here aligns residues for catalysis(75) . Reproduced from (20) .

The crystal structure of the C2 domain of synaptotagmin, elucidated by Sprang and co-workers(17) , reveals how the other half of the regulatory region of protein kinase C folds. Fig. 2B shows the core of this domain (``C2 key''): 5 aspartate residues form the Ca -binding site (pink); on the back face of this cleft are bulky aromatics (purple) adjacent to a basic surface formed by two strands (blue). Sossin and Schwartz (18) noted that novel protein kinase Cs contain a C2 domain. The solved structure elucidates how these protein kinase Cs can have this domain without being Ca -regulated; the C2 domain of novel protein kinase Cs has the conserved residues that maintain the fold of the domain (e.g.Fig. 2B, orange), but the coordinating oxygens in the Ca -binding site are mainly absent(9) . A modeled structure of the catalytic domain of protein kinase C II, with bound pseudosubstrate, based on the crystal structure of protein kinase A with bound inhibitory peptide (19) is shown in Fig. 2C(20) . The primary sequence of the kinase core of conventional protein kinase Cs is approximately 40% identical to that of protein kinase A's core. The N-terminal residue of the model is just before the hinge

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region; the peptide chain would continue on to the C2 and then C1 domains and then connect to the pseudosubstrate. Modeling of the latter in the substrate binding cavity reveals that it is held there, in part, by a cluster of acidic residues that is unique to the protein kinase C family(20) . The pseudosubstrate sequence was identified by House and Kemp (10) based on the ability of a synthetic peptide of this sequence to inhibit protein kinase C.

Function Enzymology The chemistry of protein kinase C's catalytic core is similar to that of the archetypal kinase, protein kinase A. The kinase uses MgATP as substrate, with a K for ATP in the low µM range(21) . The enzyme's maximal catalytic rate and K for a peptide substrate based on its pseudosubstrate have been reported to be 8 µmol of phosphate hydrolyzed per min per mg of protein (corresponding to 10 reactions/s) and 0.2 µM, respectively(10) . This corresponds to a k /K of 5 10 s M , revealing remarkable efficiency. Most other synthetic peptides have K values in the low µM range and V values typically ranging from 1 to 8 µmol min mg (22, 23, 24, 25, 26) , suggesting that a k /K of 10 s M is more representative of this family of enzymes. The k /K of protein kinase A for kemptide, a synthetic peptide based on the kinase's consensus phosphorylation sequence(27) , is comparable(28) . Protein kinase C typically phosphorylates serine or threonine residues in basic sequences but displays significantly less specificity than protein kinase A(29) . First, unlike protein kinase A(29) , no clear requirements for positive charge at specific positions are apparent from analysis of sequences around phosphorylation sites (30, 31, 32) or from analysis of synthetic peptide substrates(23, 26, 33) . Second, protein kinase C displays lower stereospecificity than protein kinase A (25) , phosphorylating both Dand L-stereoisomers of configurational isomers of a number of alcohols(24) . Lawrence and coworkers (24) have suggested that protein kinase C's lack of stereospecificity could reflect substrate binding in either direction (i.e. C to N or N to C) in the substrate-binding cavity(24) . Protein kinase C also autophosphorylates in vitro(34, 35) by an intramolecular mechanism (36) at the N terminus, hinge, and C terminus(37) ; the latter site is a poor in vitro site because it is almost quantitatively phosphorylated in vivo (see below). In addition to catalyzing phosphorylation reactions, protein kinase C has ATPase and phosphatase activity. The enzyme catalyzes a cofactor-dependent and substrate-stimulated hydrolysis of ATP(38) , and it can work backwards (i.e. as a phosphatase) in the presence of excess ADP. ( ) Biological Function Given the plethora of substrates and the effectiveness of phorbol esters in modulating diverse cellular responses, a multiplicity of functions have been ascribed to protein kinase C(4) . Recurring themes are that protein kinase C is involved in receptor desensitization, in modulating membrane structure events, in regulating transcription, in mediating immune responses, in regulating cell growth, and in learning and memory among many other functions. These and the functions of specific isozymes are described in a number of excellent reviews(1, 2, 3, 4, 39) . A key regulator of protein kinase C function in vivo is likely to be subcellular distribution of both the

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enzyme and substrate (40) . Protein kinase C isozymes are distributed differentially throughout the cell (and differently among many cell types)(39) , and a number of targetting proteins have been described (40) . Deciphering the specific functions of isozymes likely awaits the development of isozyme-specific inhibitors(41) . The application of combinatorial chemistry toward this goal has provided the first isozyme-specific inhibitor(42) ; similar specificity using antisense DNA has been demonstrated for in situ studies(43) .

Regulation The function of protein kinase C is regulated by two equally important mechanisms. First, the enzyme is rendered catalytically competent by phosphorylations that correctly align residues for catalysis and localize protein kinase C to the cytosol. Second, binding of ligands or, in some cases, substrate activates the enzyme by removing the pseudosubstrate from the substrate-binding site.

Pseudosubstrate Regulation Biochemical experiments have established that, as predicted(10) , activation of protein kinase C is accompanied by removal of its pseudosubstrate from the kinase core(20, 44) . Specifically, the basic pseudosubstrate is protected from proteolysis when the enzyme is not catalytically active but becomes highly sensitive to proteolysis by trypsin or endoproteinase Arg-C upon activation(44) . Importantly, the pseudosubstrate is unmasked whether protein kinase C is activated by conventional (phosphatidylserine, diacylglycerol, and Ca ), non-conventional (e.g. short chained phosphatidylcholines(45) ), or cofactorindependent substrates (e.g. protamine(46) )(20) . Consistent with this, incubation of protein kinase C with an antibody directed against the pseudosubstrate was shown to activate the enzyme, presumably by removing the pseudosubstrate from the active site(47) . Diacylglycerol and Phorbol Esters Since the discovery that phorbol esters cause protein kinase C to ``translocate'' to membranes (48, 49, 50) , this and the accompanying activation by these molecules and diacylglycerols have been the subject of extensive investigations(7, 51) . Taken together with recent molecular biological(52, 53, 54, 55, 56) , structural(15) , and biophysical studies(57, 58, 59) , a fairly good understanding of the mechanism for the effects of these C1 ligands on protein kinase C function has emerged. Diacylglycerol and phorbol esters serve as hydrophobic anchors to recruit protein kinase C to the membrane; they cause a dramatic increase in the enzyme's membrane affinity ( )that is linearly related to the mol fraction C1 ligand in the bilayer, is reversible, and can occur in the absence of acidic lipids and C2 domain interactions( )(55, 57, 58, 59, 60, 61) . Differences in the biological action of these two classes of ligands are accounted for by the 2 orders of magnitude increased potency of phorbol esters compared with diacylglycerol (58) and the long life of phorbol esters in cells. The phorbol ester domain structure suggests how the membrane anchor works; by capping the hydrophilic ligand groove, phorbol ester binding alters the surface hydrophobicity of the domain, thus promoting the membrane interaction in the absence of conformational changes(15) .

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In addition to increasing protein kinase C's membrane affinity, C1 ligands may also stabilize the active conformation of protein kinase C. Diacylglycerol doubles the catalytic efficiency of enzyme that is bound to phosphatidylserine(57, 59, 62, 63) ; it also stimulates the activation promoted by fatty acids (3) and short chained phosphatidylcholines(45) . C1 ligands markedly reduce the concentration of Ca required for the phosphatidylserine-dependent activation of protein kinase C (64) . The molecular basis for this does not arise from allosteric interactions between the C1 and C2 domain sites; Ca has no effect on protein kinase C's affinity for either C1 ligand (59, 65) . Rather, the apparent synergy between these two activators arises because each, by separate mechanisms, increases the affinity of protein kinase C for membranes. Consistent with no allosteric interactions, the structure of the phorbol ester-binding domain is unchanged by phorbol ester binding (15) . Phosphatidylserine The requirement for a ``membrane factor'' to activate protein kinase C was established shortly after the discovery of the enzyme(46) . Pioneering work by Bell and co-workers in the mid-1980s established the remarkable specificity for the serine headgroup for activation(7) . The mechanism for the phosphatidylserine-dependent stimulation is now well characterized as a result of binding measurements that have allowed the effect of phospholipid headgroup structure, diacylglycerol, and Ca on the interaction of protein kinase C with membranes to be dissected out(6) . Studies with lipid in bilayers or detergent-lipid mixed micelles have established that the phospholipid regulation and accompanying conformational changes depend on phospholipid structure rather than membrane structure(6) , although the latter does modulate enzyme activity(5, 66) . In the absence of C1 ligands, protein kinase C binds acidic lipids with little selectivity for the headgroup beyond the requirement for negative charge (59) (this interaction is Ca -regulated for conventional protein kinase Cs; see next section). This binding is of relatively low affinity, is sensitive to ionic strength, is accompanied by a conformational change that exposes the hinge region to proteolysis, and is typically not accompanied by much activation or pseudosubstrate exposure (Fig. 3, top middle)(44, 59, 60) . Note that the hinge exposure is independent of the active state of the kinase, reflecting rather the ``membrane-bound conformation'' of the enzyme (67) .

Figure 3: Model for the regulation of protein kinase C by 1) phosphorylation and 2) membrane binding and pseudosubstrate release. Newly synthesized protein kinase C (PKC) associates with the detergent-insoluble fraction of cells (72) (bottom left). It is processed to the mature, cytosolic form by three functionally distinct phosphorylations: transphosphorylation at the activation loop to render the kinase catalytically competent (Thr-500 in II); an autophosphorylation at the C terminus (Thr-641 in II) that stabilizes the catalytically competent conformation(73) ; and a second autophosphorylation at the C terminus (Ser-660 in II) that releases protein kinase C into the cytosol(73) . This triple phosphorylated mature form is inactive because the pseudosubstrate occupies the substrate-binding cavity (middle). Generation of diacylglycerol (DG) causes the affinity of protein kinase C for membranes to increase dramatically. Membrane translocation is mediated by diacylglycerol binding to the C1 domain and phosphatidylserine (PS) binding to the C2 domain (top right). The affinity for acidic lipids is increased by Ca for conventional protein kinase Cs, likely by structuring the lipid-binding surface, but not for novel protein kinase Cs, whose lipid-binding surface may already be structured. Protein kinase C can bind to membranes with low affinity with either

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C1 domain ligands (not shown) or with C2 domain ligands (top middle). However, it is the high affinity binding (top left) mediated by both domains that results in pseudosubstrate release and maximal activation. Asterisks indicate the exposed hinge, which becomes proteolytically labile upon membrane binding (independently of pseudosubstrate release(67) ), and the exposed pseudosubstrate, which becomes proteolytically labile upon activation (independently of membrane binding(20) ).

The presence of diacylglycerol causes a striking and selective increase in conventional and novel protein kinase C's affinity for phosphatidylserine that is accompanied by activation and pseudosubstrate release (Fig. 3, top left)(6) . This high affinity interaction is 1 order of magnitude stronger for surfaces containing phosphatidyl-L-serine compared with other acidic lipids such as phosphatidyl-D-serine (59) . Thus, specific structural elements of the L-serine headgroup are required for the high affinity binding of protein kinase C to membranes containing C1 ligands. Because phosphatidylserine promotes the binding of phorbol esters to a single recombinant Cys-rich domain(55) , the specificity may arise from additional interactions of the L-serine headgroup with the C1 domain or with new surfaces created at the C1-C2 interface. Kinetic studies suggest that protein kinase C interacts cooperatively with multiple phosphatidylserine molecules(6, 7) . Calcium Ions Ca increases the affinity of conventional protein kinase Cs for negatively charged lipids(69) , with no selectivity for headgroup other than the requirement for negative charge(59) . This increase varies linearly with Ca concentration in the low µM to submillimolar range(65) , consistent with the single Ca -binding site apparent in the C2 domain structure(17) . The dissociation constant of Ca from membrane-bound protein kinase C has been calculated to be approximately 700 nM, and that from soluble protein kinase C has been estimated to be 3 mM(65) . The C2 domain structure provides tantalizing insight into how Ca might increase the affinity of conventional, but not novel, protein kinase Cs for acidic lipids. For conventional protein kinase Cs, binding of Ca to the aspartate-lined ``mouth'' (Fig. 2B) might clamp together the upper and lower lobes, thus orienting the bulky aromatics on the back face of the mouth to interact with the membrane and orienting the basic face of the sheet behind the site to interact with lipid headgroups. For novel protein kinase Cs (such as ), the presence of an Arg instead of an Asp at one of the positions in the site (9) might cause the mouth to adopt the closed conformation, so that the domain is already structured to bind acidic lipids. C1 ligands would then target novel protein kinase Cs to membranes, with the reduction in dimensionality promoting the binding of the C2 domain to acidic lipids. Consistent with this, the lipid regulation of novel protein kinase Cs is the same as that for conventional protein kinase Cs, except that it occurs in the absence of Ca (70) . Substrates Protein kinase C phosphorylates a number of Arg-rich proteins in a cofactor-independent manner(46, 71) . These substrates, alone, are able to displace the pseudosubstrate from the kinase core(20) . One possibility is that these Arg-rich peptides neutralize the acidic patch that appears to maintain the pseudosubstrate in the active site(20) , thus releasing the basic pseudosubstrate by competing for contacts. In this regard, the ability of Arg-rich peptides to promote protein kinase C autophosphorylation (rather than compete with it) led to the suggestion that Arg-rich molecules bind to a separate site from the active site(71) . An intriguing possibility is that the acidic cluster interacts with Arg-rich sequences of cytoskeletal proteins, thus allowing activation distal from the lipid bilayer.

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Regulation by Phosphorylation in Vivo Pulse-chase experiments by Fabbro and co-workers (72) provided the first evidence that protein kinase C is phosphorylated in vivo. Specifically, they showed that protein kinase C is first synthesized as an inactive, dephosphorylated precursor with an apparent M of 74 kDa; this was chased to a transient 77kDa phospho-form and then to the final 80-kDa mature form. Mass spectrometry has recently revealed that protein kinase C is modified by three phosphorylations in vivo (73, 74). The differential dephosphorylation of these sites by protein phosphatases 1 and 2A(75) , as well as analysis of phosphorylation site mutants(76, 77) , has allowed the function of each phosphorylation to be identified (73) . A model consistent with biochemical data is presented in the lower half of Fig. 3. Newly synthesized protein kinase C associates with a detergent-insoluble cell fraction(72) ; it is rendered catalytically competent upon phosphorylation by a putative protein kinase C kinase on its activation loop (Fig. 2C). Negative charge on this loop at the entrance to the active site correctly aligns residues involved in catalysis in diverse kinases (11) ; replacement of the phosphorylated residue (Thr-500) with Glu in protein kinase C II results in activatable enzyme (77) whereas replacement with neutral nonphosphorylatable residues in this isozyme (77) or protein kinase C (76) results in kinase that cannot be activated. The first consequence of the transphosphorylation appears to be autophosphorylation at the C terminus of the kinase; this residue is Thr-641 in protein kinase C II (9 residues removed from the C terminus of the model in Fig. 2C)(73, 74) . Phosphorylation here likely stabilizes the catalytically competent conformation of the kinase as it replaces the requirement for negative charge at the activation loop(73) ; this phosphorylation causes the first detectable shift in electrophoretic mobility(73, 75) . Last, the enzyme autophosphorylates further along the C terminus (Ser-660 in protein kinase C II) in a motif shared by several other kinases(73) ; this phosphorylation causes the final shift in electrophoretic mobility and releases the mature enzyme into the cytosol(73, 75) . It is this 80-kDa form, localized to the detergent-soluble fraction, that has been extensively purified and studied in vitro. Curiously, it is only half-phosphorylated at the activation loop (but quantitatively phosphorylated at the two C-terminal sites) (73) , suggesting that dephosphorylation/transphosphorylation at this position may regulate the kinase in response to stimuli. The mature form then translocates to the membrane and undergoes the pseudosubstrate regulation discussed above.

Conclusion Protein kinase C is regulated by two distinct mechanisms: by phosphorylation which regulates the active site and subcellular localization of the enzyme, and by second messengers which promote protein kinase C's membrane association and resulting pseudosubstrate exposure. Regulation by two independent mechanisms may provide exquisite fine-tuning for this family of enzymes, ensuring low basal activity in the midst of complex intracellular signaling pathways.

FOOTNOTES *

This minireview will be reprinted in the 1995 Minireview Compendium, which will be available in December, 1995. This research was supported in part by National Institutes of Health Grant

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GM 43154, the Searle Scholars Program, and a National Science Foundation Young Investigator Award. ()

A. C. Newton, unpublished data.

() The dissociation constant of phorbol myristate acetate from membrane-bound protein kinase C, separated from all other interactions, has recently been measured as 1.5 10 mol % relative to membrane lipids; that for diacylglycerol is 250 times higher (M. Mosior and A. C. Newton, Biochemistry, in press). ()

M. Mosior and A. C. Newton, Biochemistry, in press.

ACKNOWLEDGEMENTS I thank members of my laboratory for critically reading this manuscript and for many helpful discussions.

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R. Zeidman, U. Troller, A. Raghunath, S. Pahlman, and C. Larsson Protein Kinase Cepsilon Actin-binding Site Is Important for Neurite Outgrowth during Neuronal Differentiation Mol. Biol. Cell, January 1, 2002; 13(1): 12 - 24. [Abstract] [Full Text] [PDF]

D. ZOUKHRI, R. R. HODGES, C. SERGHERAERT, and D. A. DARTT Lacrimal Gland Functions Are Differentially Controlled by Protein Kinase C Isoforms Ann. N.Y. Acad. Sci., April 15, 1998; 842(1): 217 - 220. [Full Text] [PDF]

K. Yoshida and D. Kufe Negative Regulation of the SHPTP1 Protein Tyrosine Phosphatase by Protein Kinase C delta in Response to DNA Damage Mol. Pharmacol., December 1, 2001; 60(6): 1431 - 1438. [Abstract] [Full Text] [PDF]

M. S. Song, Y. K. Park, J.-H. Lee, and K. Park Induction of Glucose-regulated Protein 78 by Chronic Hypoxia in Human Gastric Tumor Cells through a Protein Kinase C{epsilon}/ERK/AP-1 Signaling Cascade Cancer Res., November 1, 2001; 61(22): 8322 - 8330. [Abstract] [Full Text] [PDF]

J. P. Alexander and T. S. Acott Involvement of Protein Kinase C in TNF{alpha} Regulation of

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Trabecular Matrix Metalloproteinases and TIMPs Invest. Ophthalmol. Vis. Sci., November 1, 2001; 42(12): 2831 - 2838. [Abstract] [Full Text] [PDF]

E. Zhukova, J. Sinnett-Smith, and E. Rozengurt Protein Kinase D Potentiates DNA Synthesis and Cell Proliferation Induced by Bombesin, Vasopressin, or Phorbol Esters in Swiss 3T3 Cells J. Biol. Chem., October 26, 2001; 276(43): 40298 - 40305. [Abstract] [Full Text] [PDF]

K. Takekoshi, K. Ishii, T. Nanmoku, S. Shibuya, Y. Kawakami, K. Isobe, and T. Nakai Leptin Stimulates Catecholamine Synthesis in a PKC-Dependent Manner in Cultured Porcine Adrenal Medullary Chromaffin Cells Endocrinology, November 1, 2001; 142(11): 4861 - 4871. [Abstract] [Full Text] [PDF]

J. Yuan, L. W. Slice, and E. Rozengurt Activation of Protein Kinase D by Signaling through Rho and the alpha Subunit of the Heterotrimeric G Protein G13 J. Biol. Chem., October 19, 2001; 276(42): 38619 - 38627. [Abstract] [Full Text] [PDF]

O. Rey, S. H. Young, D. Cantrell, and E. Rozengurt Rapid Protein Kinase D Translocation in Response to G Proteincoupled Receptor Activation. DEPENDENCE ON PROTEIN KINASE C J. Biol. Chem., August 31, 2001; 276(35): 32616 - 32626. [Abstract] [Full Text] [PDF]

R. Hattori, H. Otani, T. Uchiyama, H. Imamura, J. Cui, N. Maulik, G. A. Cordis, L. Zhu, and D. K. Das Src tyrosine kinase is the trigger but not the mediator of ischemic preconditioning Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1066 1074. [Abstract] [Full Text] [PDF]

K. C. Das, P. M. B. Pahl, X.-L. Guo, and C. W. White

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Induction of Peroxiredoxin Gene Expression by Oxygen in Lungs of Newborn Primates Am. J. Respir. Cell Mol. Biol., August 1, 2001; 25(2): 226 - 232. [Abstract] [Full Text] [PDF]

E. G. Stebbins and D. Mochly-Rosen Binding Specificity for RACK1 Resides in the V5 Region of beta II Protein Kinase C J. Biol. Chem., August 10, 2001; 276(32): 29644 - 29650. [Abstract] [Full Text] [PDF]

P. S. Lorenzo, K. Bogi, K. M. Hughes, M. Beheshti, D. Bhattacharyya, S. H. Garfield, G. R. Pettit, and P. M. Blumberg Differential Roles of the Tandem C1 Domains of Protein Kinase C {{delta}} in the Biphasic Down-Regulation Induced by Bryostatin 1 Cancer Res., December 1, 1999; 59(24): 6137 - 6144. [Abstract] [Full Text] [PDF]

P. J. Reddig, N. E. Dreckschimdt, H. Ahrens, R. Simsiman, C.-P. Tseng, J. Zou, T. D. Oberley, and A. K. Verma Transgenic Mice Overexpressing Protein Kinase C{{delta}} in the Epidermis Are Resistant to Skin Tumor Promotion by 12-OTetradecanoylphorbol-13-acetate Cancer Res., November 1, 1999; 59(22): 5710 - 5718. [Abstract] [Full Text] [PDF]

H.-W. Lee, L. Smith, G. R. Pettit, and J. B. Smith Bryostatin 1 and Phorbol Ester Down-Modulate Protein Kinase Calpha and -epsilon via the Ubiquitin/Proteasome Pathway in Human Fibroblasts Mol. Pharmacol., March 1, 1997; 51(3): 439 - 447. [Abstract] [Full Text] [PDF]

D. H. Korzick, D. A. Holiman, M. O. Boluyt, M. H. Laughlin, and E. G. Lakatta Diminished {alpha}1-adrenergic-mediated contraction and translocation of PKC in senescent rat heart Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H581 - 589. [Abstract] [Full Text] [PDF]

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W. Li, J. Zhang, D. P. Bottaro, W. Li, and J. H. Pierce Identification of Serine 643 of Protein Kinase C-delta as an Important Autophosphorylation Site for Its Enzymatic Activity J. Biol. Chem., September 26, 1997; 272(39): 24550 - 24555. [Abstract] [Full Text] [PDF]

L. R. James, A. Ingram, H. Ly, K. Thai, L. Cai, and J. W. Scholey Angiotensin II activates the GFAT promoter in mesangial cells Am J Physiol Renal Physiol, July 1, 2001; 281(1): F151 - 162. [Abstract] [Full Text] [PDF]

R. Mandil, E. Ashkenazi, M. Blass, I. Kronfeld, G. Kazimirsky, G. Rosenthal, F. Umansky, P. S. Lorenzo, P. M. Blumberg, and C. Brodie Protein Kinase C{{alpha}} and Protein Kinase C{{delta}} Play Opposite Roles in the Proliferation and Apoptosis of Glioma Cells Cancer Res., June 1, 2001; 61(11): 4612 - 4619. [Abstract] [Full Text] [PDF]

R. Giet and C. Prigent The non-catalytic domain of the Xenopus laevis auroraA kinase localises the protein to the centrosome J. Cell Sci., January 6, 2001; 114(11): 2095 - 2104. [Abstract] [Full Text] [PDF]

D Schmalz, F Hucho, and K Buchner Nuclear import of protein kinase C occurs by a mechanism distinct from the mechanism used by proteins with a classical nuclear localization signal J. Cell Sci., January 7, 1998; 111(13): 1823 - 1830. [Abstract] [PDF]

S. Ito, H. Kume, H. Honjo, H. Katoh, I. Kodama, K. Yamaki, and H. Hayashi Possible involvement of Rho kinase in Ca2+ sensitization and mobilization by MCh in tracheal smooth muscle Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1218 - 1224. [Abstract] [Full Text]

Y. Ikeda, G. S. Olsen, E. Ziv, L. L. Hansen, A. K. Busch, B. F. Hansen, E.

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Shafrir, and L. Mosthaf-Seedorf Cellular Mechanism of Nutritionally Induced Insulin Resistance in Psammomys Obesus: Overexpression of Protein Kinase C {varepsilon} in Skeletal Muscle Precedes the Onset of Hyperinsulinemia and Hyperglycemia Diabetes, March 1, 2001; 50(3): 584 - 592. [Abstract] [Full Text]

Y.-F. Liu, K. Paz, A. Herschkovitz, A. Alt, T. Tennenbaum, S. R. Sampson, M. Ohba, T. Kuroki, D. LeRoith, and Y. Zick Insulin Stimulates PKCzeta -mediated Phosphorylation of Insulin Receptor Substrate-1 (IRS-1). A SELF-ATTENUATED MECHANISM TO NEGATIVELY REGULATE THE FUNCTION OF IRS PROTEINS J. Biol. Chem., April 20, 2001; 276(17): 14459 - 14465. [Abstract] [Full Text] [PDF]

A. C. Megson, E. M. Walker, and S. J. Hill Role of Protein Kinase Calpha in Signaling from the Histamine H1 Receptor to the Nucleus Mol. Pharmacol., April 16, 2001; 59(5): 1012 - 1021. [Abstract] [Full Text]

E. L. Deszo, D. K. Brake, K. A. Cengel, K. W. Kelley, and G. G. Freund CD45 Negatively Regulates Monocytic Cell Differentiation by Inhibiting Phorbol 12-Myristate 13-Acetate-dependent Activation and Tyrosine Phosphorylation of Protein Kinase Cdelta J. Biol. Chem., March 23, 2001; 276(13): 10212 - 10217. [Abstract] [Full Text] [PDF]

B. A. Niemeyer, C. Bergs, U. Wissenbach, V. Flockerzi, and C. Trost Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and calmodulin PNAS, March 13, 2001; 98(6): 3600 - 3605. [Abstract] [Full Text] [PDF]

T. Chiu and E. Rozengurt PKD in intestinal epithelial cells: rapid activation by phorbol esters, LPA, and angiotensin through PKC Am J Physiol Cell Physiol, April 1, 2001; 280(4): C929 - 942. [Abstract] [Full Text]

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L. Paolucci and E. Rozengurt Protein Kinase D in Small Cell Lung Cancer Cells: Rapid Activation through Protein Kinase C Cancer Res., February 1, 1999; 59(3): 572 - 577. [Abstract] [Full Text] [PDF]

F. Manseau, X. Fan, T. Hueftlein, W. S. Sossin, and V. F. Castellucci Ca2+-Independent Protein Kinase C Apl II Mediates the Serotonin-Induced Facilitation at Depressed Aplysia Sensorimotor Synapses J. Neurosci., February 15, 2001; 21(4): 1247 - 1256. [Abstract] [Full Text]

M. M. Monick, J. M. Staber, K. W. Thomas, and G. W. Hunninghake Respiratory Syncytial Virus Infection Results in Activation of Multiple Protein Kinase C Isoforms Leading to Activation of Mitogen-Activated Protein Kinase J. Immunol., February 15, 2001; 166(4): 2681 - 2687. [Abstract] [Full Text] [PDF]

A. M. Pepio and W. S. Sossin Membrane Translocation of Novel Protein Kinase Cs Is Regulated by Phosphorylation of the C2 Domain J. Biol. Chem., February 2, 2001; 276(6): 3846 - 3855. [Abstract] [Full Text] [PDF]

L. Bittova, R. V. Stahelin, and W. Cho Roles of Ionic Residues of the C1 Domain in Protein Kinase Calpha Activation and the Origin of Phosphatidylserine Specificity J. Biol. Chem., February 2, 2001; 276(6): 4218 - 4226. [Abstract] [Full Text] [PDF]

J. NEUZIL, T. WEBER, A. SCHRÖDER, M. LU, G. OSTERMANN, N. GELLERT, G. C. MAYNE, B. OLEJNICKA, A. NÈGRE-SALVAYRE, M. STÍCHA, R. J. COFFEY, and C. WEBER Induction of cancer cell apoptosis by {alpha}-tocopheryl succinate: molecular pathways and structural requirements FASEB J, February 1, 2001; 15(2): 403 - 415. [Abstract] [Full Text]

C. Brodie, K. Bogi, P. Acs, P. Lazarovici, G. Petrovics, W. B. Anderson,

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and P. M. Blumberg Protein Kinase C-{{epsilon}} Plays a Role in Neurite Outgrowth in Response to Epidermal Growth Factor and Nerve Growth Factor in PC12 Cells Cell Growth Differ., March 1, 1999; 10(3): 183 - 191. [Abstract] [Full Text]

P. J. Reddig, N. E. Dreckschmidt, J. Zou, S. E. Bourguignon, T. D. Oberley, and A. K. Verma Transgenic Mice Overexpressing Protein Kinase C{{epsilon}} in Their Epidermis Exhibit Reduced Papilloma Burden but Enhanced Carcinoma Formation after Tumor Promotion Cancer Res., February 1, 2000; 60(3): 595 - 602. [Abstract] [Full Text]

L. Smith, L. Chen, M. E. Reyland, T. A. DeVries, R. V. Talanian, S. Omura, and J. B. Smith Activation of Atypical Protein Kinase C zeta by Caspase Processing and Degradation by the Ubiquitin-Proteasome System J. Biol. Chem., December 15, 2000; 275(51): 40620 - 40627. [Abstract] [Full Text] [PDF]

A. Ray, A. P. Fields, and B. K. Ray Activation of Transcription Factor SAF Involves Its Phosphorylation by Protein Kinase C J. Biol. Chem., December 8, 2000; 275(50): 39727 - 39733. [Abstract] [Full Text] [PDF]

M. A. Graham, I. Rawe, D. A. Dartt, and N. C. Joyce Protein Kinase C Regulation of Corneal Endothelial Cell Proliferation and Cell Cycle Invest. Ophthalmol. Vis. Sci., December 1, 2000; 41(13): 4124 - 4132. [Abstract] [Full Text]

C. Bertolotto, L. Maulon, N. Filippa, G. Baier, and P. Auberger Protein Kinase C theta and epsilon Promote T-cell Survival by a Rsk-dependent Phosphorylation and Inactivation of BAD J. Biol. Chem., November 17, 2000; 275(47): 37246 - 37250. [Abstract] [Full Text] [PDF]

S. Nowicki, M. S. Kruse, H. Brismar, and A. Aperia

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Dopamine-induced translocation of protein kinase C isoforms visualized in renal epithelial cells Am J Physiol Cell Physiol, December 1, 2000; 279(6): C1812 - 1818. [Abstract] [Full Text]

H.-C. Huang, T. Nguyen, and C. B. Pickett Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2 PNAS, November 7, 2000; 97(23): 12475 - 12480. [Abstract] [Full Text] [PDF]

P. Banky, M. G. Newlon, M. Roy, S. Garrod, S. S. Taylor, and P. A. Jennings Isoform-specific Differences between the Type Ialpha and IIalpha Cyclic AMP-dependent Protein Kinase Anchoring Domains Revealed by Solution NMR J. Biol. Chem., November 3, 2000; 275(45): 35146 - 35152. [Abstract] [Full Text] [PDF]

I. Kronfeld, G. Kazimirsky, P. S. Lorenzo, S. H. Garfield, P. M. Blumberg, and C. Brodie Phosphorylation of Protein Kinase Cdelta on Distinct Tyrosine Residues Regulates Specific Cellular Functions J. Biol. Chem., November 3, 2000; 275(45): 35491 - 35498. [Abstract] [Full Text] [PDF]

K. Yano, J. R. Bauchat, M. B. Liimatta, D. R. Clemmons, and C. Duan Down-Regulation of Protein Kinase C Inhibits Insulin-Like Growth Factor I-Induced Vascular Smooth Muscle Cell Proliferation, Migration, and Gene Expression Endocrinology, October 1, 1999; 140(10): 4622 - 4632. [Abstract] [Full Text]

N. Fernandez, M. J. Caloca, G. V. Prendergast, J. L. Meinkoth, and M. G. Kazanietz Atypical Protein Kinase C-{zeta} Stimulates ThyrotropinIndependent Proliferation in Rat Thyroid Cells Endocrinology, January 1, 2000; 141(1): 146 - 152. [Abstract] [Full Text]

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S. Migliaccio, T. F. Washburn, S. Fillo, H. Rivera, A. Teti, K. S. Korach, and W. C. Wetsel Modulation of Estrogen Receptor Levels in Mouse Uterus by Protein Kinase C Isoenzymes Endocrinology, November 1, 1998; 139(11): 4598 - 4606. [Abstract] [Full Text]

M. A. Ansonoff and A. M. Etgen Estradiol Elevates Protein Kinase C Catalytic Activity in the Preoptic Area of Female Rats Endocrinology, July 1, 1998; 139(7): 3050 - 3056. [Abstract] [Full Text] [PDF]

B. D. Saunders, E. Sabbagh, W. W. Chin, and U. B. Kaiser Differential Use of Signal Transduction Pathways in the Gonadotropin-Releasing Hormone-Mediated Regulation of Gonadotropin Subunit Gene Expression Endocrinology, April 1, 1998; 139(4): 1835 - 1843. [Abstract] [Full Text]

M. L. G. Lamm, D. D. Long, S. M. Goodwin, and C. Lee Transforming Growth Factor-{beta}1 Inhibits Membrane Association of Protein Kinase C{alpha} in a Human Prostate Cancer Cell Line, PC3 Endocrinology, November 1, 1997; 138(11): 4657 - 4664. [Abstract] [Full Text]

L. Chen, L. Smith, M. R. Johnson, K. Wang, R. B. Diasio, and J. B. Smith Activation of Protein Kinase C Induces Nuclear Translocation of RFX1 and Down-regulates c-myc via an Intron 1 X Box in Undifferentiated Leukemia HL-60 Cells J. Biol. Chem., October 6, 2000; 275(41): 32227 - 32233. [Abstract] [Full Text] [PDF]

R. N. A. H. Lewis and R. N. McElhaney Calorimetric and Spectroscopic Studies of the Thermotropic Phase Behavior of Lipid Bilayer Model Membranes Composed of a Homologous Series of Linear Saturated Phosphatidylserines Biophys. J., October 1, 2000; 79(4): 2043 - 2055. [Abstract] [Full Text]

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C. Yue, C.-Y. Ku, M. Liu, M. I. Simon, and B. M. Sanborn Molecular Mechanism of the Inhibition of Phospholipase C beta 3 by Protein Kinase C J. Biol. Chem., September 22, 2000; 275(39): 30220 - 30225. [Abstract] [Full Text] [PDF]

J. B. Nixon and L. C. McPhail Protein Kinase C (PKC) Isoforms Translocate to Triton-Insoluble Fractions in Stimulated Human Neutrophils: Correlation of Conventional PKC with Activation of NADPH Oxidase J. Immunol., October 15, 1999; 163(8): 4574 - 4582. [Abstract] [Full Text] [PDF]

J. H. Brumell, J. C. Howard, K. Craig, S. Grinstein, A. D. Schreiber, and M. Tyers Expression of the Protein Kinase C Substrate Pleckstrin in Macrophages: Association with Phagosomal Membranes J. Immunol., September 15, 1999; 163(6): 3388 - 3395. [Abstract] [Full Text] [PDF]

L. B. King, A. Norvell, and J. G. Monroe Antigen Receptor-Induced Signal Transduction Imbalances Associated with the Negative Selection of Immature B Cells J. Immunol., March 1, 1999; 162(5): 2655 - 2662. [Abstract] [Full Text] [PDF]

M. Giroux and A. Descoteaux Cyclooxygenase-2 Expression in Macrophages: Modulation by Protein Kinase C-{alpha} J. Immunol., October 1, 2000; 165(7): 3985 - 3991. [Abstract] [Full Text] [PDF]

H. Goldfine, S. J. Wadsworth, and N. C. Johnston Activation of Host Phospholipases C and D in Macrophages after Infection with Listeria monocytogenes Infect. Immun., October 1, 2000; 68(10): 5735 - 5741. [Abstract] [Full Text] [PDF]

R. N. A. H. Lewis and R. N. McElhaney Surface Charge Markedly Attenuates the Nonlamellar PhaseForming Propensities of Lipid Bilayer Membranes: Calorimetric

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and 31P-Nuclear Magnetic Resonance Studies of Mixtures of Cationic, Anionic, and Zwitterionic Lipids Biophys. J., September 1, 2000; 79(3): 1455 - 1464. [Abstract] [Full Text]

A. Blaukat, A. Barac, M. J. Cross, S. Offermanns, and I. Dikic G Protein-Coupled Receptor-Mediated Mitogen-Activated Protein Kinase Activation through Cooperation of Galpha q and Galpha i Signals Mol. Cell. Biol., September 15, 2000; 20(18): 6837 - 6848. [Abstract] [Full Text]

R. A. Hopper, C. R. Forrest, H. Xu, A. Zhong, W. He, J. Rutka, P. Neligan, and C. Y. Pang Role and mechanism of PKC in ischemic preconditioning of pig skeletal muscle against infarction Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2000; 279 (2): R666 - 676. [Abstract] [Full Text]

B. L.J. Webb, S. J. Hirst, and M. A. Giembycz Protein kinase C isoenzymes: a review of their structure, regulation and role in regulating airways smooth muscle tone and mitogenesis Br. J. Pharmacol., August 7, 2000; 130(7): 1433 - 1452. [Abstract] [Full Text]

L. T. Knapp and E. Klann Superoxide-induced Stimulation of Protein Kinase C via Thiol Modification and Modulation of Zinc Content J. Biol. Chem., July 28, 2000; 275(31): 24136 - 24145. [Abstract] [Full Text] [PDF]

S. C. Frasch, P. M. Henson, J. M. Kailey, D. A. Richter, M. S. Janes, V. A. Fadok, and D. L. Bratton Regulation of Phospholipid Scramblase Activity during Apoptosis and Cell Activation by Protein Kinase Cdelta J. Biol. Chem., July 21, 2000; 275(30): 23065 - 23073. [Abstract] [Full Text] [PDF]

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A. Radominska-Pandya, G. Chen, P. J. Czernik, J. M. Little, V. M. Samokyszyn, C. A. Carter, and G.{m. d.}y. Nowak Direct Interaction of All-trans-retinoic Acid with Protein Kinase C (PKC). IMPLICATIONS FOR PKC SIGNALING AND CANCER THERAPY J. Biol. Chem., July 14, 2000; 275(29): 22324 - 22330. [Abstract] [Full Text] [PDF]

J. Mills and P. B. Reiner Regulation of Amyloid Precursor Protein Cleavage J. Neurochem., February 1, 1999; 72(2): 443 - 460. [Abstract] [Full Text]

U. Salli, S. Supancic, and F. Stormshak Phosphorylation of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) Protein Is Associated with Bovine Luteal Oxytocin Exocytosis Biol. Reprod., July 1, 2000; 63(1): 12 - 20. [Abstract] [Full Text]

H. L. Roderick, J. D. Lechleiter, and P. Camacho Cytosolic Phosphorylation of Calnexin Controls Intracellular Ca2+ Oscillations via an Interaction with SERCA2b J. Cell Biol., June 12, 2000; 149(6): 1235 - 1248. [Abstract] [Full Text]

K. Endo, E. Oki, V. Biedermann, H. Kojima, K. Yoshida, F.-J. Johannes, D. Kufe, and R. Datta Proteolytic Cleavage and Activation of Protein Kinase C {micro} by Caspase-3 in the Apoptotic Response of Cells to 1-beta -DArabinofuranosylcytosine and Other Genotoxic Agents J. Biol. Chem., June 9, 2000; 275(24): 18476 - 18481. [Abstract] [Full Text] [PDF]

X. Feng, K. P. Becker, S. D. Stribling, K. G. Peters, and Y. A. Hannun Regulation of Receptor-mediated Protein Kinase C Membrane Trafficking by Autophosphorylation J. Biol. Chem., May 26, 2000; 275(22): 17024 - 17034. [Abstract] [Full Text] [PDF]

W.-H. Zheng, S. Kar, and R. Quirion

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Stimulation of Protein Kinase C Modulates Insulin-like Growth Factor-1-induced Akt Activation in PC12 Cells J. Biol. Chem., April 28, 2000; 275(18): 13377 - 13385. [Abstract] [Full Text] [PDF]

P. Ács, M. Beheshti, Z. Szállási, L. Li, S. H. Yuspa, and P. M. Blumberg Effect of a tyrosine 155 to phenylalanine mutation of protein kinase C{delta} on the proliferative and tumorigenic properties of NIH 3T3 fibroblasts Carcinogenesis, May 1, 2000; 21(5): 887 - 891. [Abstract] [Full Text]

Y.-Z. Wang and J. C. Bonner Mechanism of Extracellular Signal-Regulated Kinase (ERK)-1 and ERK-2 Activation by Vanadium Pentoxide in Rat Pulmonary Myofibroblasts Am. J. Respir. Cell Mol. Biol., May 1, 2000; 22(5): 590 - 596. [Abstract] [Full Text]

P. S. Lorenzo, M. Beheshti, G. R. Pettit, J. C. Stone, and P. M. Blumberg The Guanine Nucleotide Exchange Factor RasGRP Is a High Affinity Target for Diacylglycerol and Phorbol Esters Mol. Pharmacol., May 1, 2000; 57(5): 840 - 846. [Abstract] [Full Text]

Q. J. Wang, T.-W. Fang, D. Fenick, S. Garfield, B. Bienfait, V. E. Marquez, and P. M. Blumberg The Lipophilicity of Phorbol Esters as a Critical Factor in Determining the Pattern of Translocation of Protein Kinase C delta Fused to Green Fluorescent Protein J. Biol. Chem., April 14, 2000; 275(16): 12136 - 12146. [Abstract] [Full Text] [PDF]

R. Yu, S. Mandlekar, T.-H. Tan, and A.-N. T. Kong Activation of p38 and c-Jun N-terminal Kinase Pathways and Induction of Apoptosis by Chelerythrine Do Not Require Inhibition of Protein Kinase C J. Biol. Chem., March 24, 2000; 275(13): 9612 - 9619. [Abstract] [Full Text] [PDF]

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M. P. Coghlan, M. M. Chou, and C. L. Carpenter Atypical Protein Kinases Clambda and -zeta Associate with the GTP-Binding Protein Cdc42 and Mediate Stress Fiber Loss Mol. Cell. Biol., April 15, 2000; 20(8): 2880 - 2889. [Abstract] [Full Text]

J. Wang, L. Wang, J. Zheng, J. L. Anderson, and M. L. Toews Identification of Distinct Carboxyl-Terminal Domains Mediating Internalization and Down-Regulation of the Hamster alpha 1BAdrenergic Receptor Mol. Pharmacol., April 1, 2000; 57(4): 687 - 694. [Abstract] [Full Text]

I. L. PFAFF, H.-J. WAGNER, and V. VALLON Immunolocalization of Protein Kinase C Isoenzymes {alpha}, {beta}I and {beta}II in Rat Kidney J. Am. Soc. Nephrol., September 1, 1999; 10(9): 1861 - 1873. [Abstract] [Full Text]

J. KAPOR-DREZGIC, X. ZHOU, T. BABAZONO, J. A. DLUGOSZ, T. HOHMAN, and C. WHITESIDE Effect of High Glucose on Mesangial Cell Protein Kinase C-{delta} and - is Polyol Pathway-Dependent J. Am. Soc. Nephrol., June 1, 1999; 10(6): 1193 - 1203. [Abstract] [Full Text]

V. M. Berthoud, E. M. Westphale, A. Grigoryeva, and E. C. Beyer PKC Isoenzymes in the Chicken Lens and TPA-Induced Effects on Intercellular Communication Invest. Ophthalmol. Vis. Sci., March 1, 2000; 41(3): 850 - 858. [Abstract] [Full Text]

K. Katagiri, M. Hattori, N. Minato, S.-k. Irie, K. Takatsu, and T. Kinashi Rap1 Is a Potent Activation Signal for Leukocyte FunctionAssociated Antigen 1 Distinct from Protein Kinase C and Phosphatidylinositol-3-OH Kinase Mol. Cell. Biol., March 15, 2000; 20(6): 1956 - 1969. [Abstract] [Full Text]

K.-p. Liu, S.-c. Hsiung, M. Adlersberg, T. Sacktor, M. D. Gershon, and H. Tamir

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Ca2+-Evoked Serotonin Secretion by Parafollicular Cells: Roles in Signal Transduction of Phosphatidylinositol 3'-kinase, and the gamma and zeta Isoforms of Protein Kinase C J. Neurosci., February 15, 2000; 20(4): 1365 - 1373. [Abstract] [Full Text]

R. Alcántara-Hernández, J. Vázquez-Prado, and J. A. García-Sáinz Protein phosphatase-protein kinase interplay modulates {alpha} 1b-adrenoceptor phosphorylation: effects of okadaic acid Br. J. Pharmacol., February 4, 2000; 129(4): 724 - 730. [Abstract] [Full Text]

A. Vallentin, C. Prevostel, T. Fauquier, X. Bonnefont, and D. Joubert Membrane Targeting and Cytoplasmic Sequestration in the Spatiotemporal Localization of Human Protein Kinase C alpha J. Biol. Chem., February 25, 2000; 275(8): 6014 - 6021. [Abstract] [Full Text] [PDF]

M. F. Oleksiak, S. Wu, C. Parker, S. I. Karchner, J. J. Stegeman, and D. C. Zeldin Identification, Functional Characterization, and Regulation of a New Cytochrome P450 Subfamily, the CYP2Ns J. Biol. Chem., January 28, 2000; 275(4): 2312 - 2321. [Abstract] [Full Text] [PDF]

S. Witte, M. Villalba, K. Bi, Y. Liu, N. Isakov, and A. Altman Inhibition of the c-Jun N-terminal Kinase/AP-1 and NF-kappa B Pathways by PICOT, a Novel Protein Kinase C-interacting Protein with a Thioredoxin Homology Domain J. Biol. Chem., January 21, 2000; 275(3): 1902 - 1909. [Abstract] [Full Text] [PDF]

J. Yuan, L. Slice, J. H. Walsh, and E. Rozengurt Activation of Protein Kinase D by Signaling through the alpha Subunit of the Heterotrimeric G Protein Gq J. Biol. Chem., January 21, 2000; 275(3): 2157 - 2164. [Abstract] [Full Text] [PDF]

Q. J. Wang, D. Bhattacharyya, S. Garfield, K. Nacro, V. E. Marquez, and P. M. Blumberg Differential Localization of Protein Kinase C delta by Phorbol

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Esters and Related Compounds Using a Fusion Protein with Green Fluorescent Protein J. Biol. Chem., December 24, 1999; 274(52): 37233 - 37239. [Abstract] [Full Text] [PDF]

C. Yu, J. Chen, S. Lin, J. Liu, C. C. Y. Chang, and T.-Y. Chang Human Acyl-CoA:Cholesterol Acyltransferase-1 Is a Homotetrameric Enzyme in Intact Cells and in Vitro J. Biol. Chem., December 17, 1999; 274(51): 36139 - 36145. [Abstract] [Full Text] [PDF]

J. C. Adams, J. D. Clelland, G. D.M. Collett, F. Matsumura, S. Yamashiro, and L. Zhang Cell-Matrix Adhesions Differentially Regulate Fascin Phosphorylation Mol. Biol. Cell, December 1, 1999; 10(12): 4177 - 4190. [Abstract] [Full Text]

N. Verdaguer, S. Corbalan-Garcia, W. F. Ochoa, I. Fita, and J. C. GómezFernández Ca2+ bridges the C2 membrane-binding domain of protein kinase Calpha directly to phosphatidylserine EMBO J., November 15, 1999; 18(22): 6329 - 6338. [Abstract] [Full Text]

K. Yamaki and K. Ohuchi Participation of protein kinases in staurosporine-induced interleukin-6 production by rat peritoneal macrophages Br. J. Pharmacol., July 15, 1999; 127(6): 1309 - 1316. [Abstract] [Full Text]

N. Meller, A. Altman, and N. Isakov New Perspectives on PKC{theta}, a Member of the Novel Subfamily of Protein Kinase C Stem Cells, May 1, 1998; 16(3): 178 - 192. [Abstract] [Full Text]

D.-H. Hong, G. Petrovics, W. B. Anderson, J. Forstner, and G. Forstner Induction of mucin gene expression in human colonic cell lines by PMA is dependent on PKC-epsilon

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Am J Physiol Gastrointest Liver Physiol, November 1, 1999; 277(5): G1041 - 1047. [Abstract] [Full Text]

A. Nakhost, J. R. Dyer, A. M. Pepio, X. Fan, and W. S. Sossin Protein Kinase C Phosphorylated at a Conserved Threonine Is Retained in the Cytoplasm J. Biol. Chem., October 8, 1999; 274(41): 28944 - 28949. [Abstract] [Full Text] [PDF]

M. Heinrich, M. Wickel, W. Schneider-Brachert, C. Sandberg, J. Gahr, R. Schwandner, T. Weber, J. Brunner, M. Krönke, and S. Schütze Cathepsin D targeted by acid sphingomyelinase-derived ceramide EMBO J., October 1, 1999; 18(19): 5252 - 5263. [Abstract] [Full Text]

D. RON and M. G. KAZANIETZ New insights into the regulation of protein kinase C and novel phorbol ester receptors FASEB J, October 1, 1999; 13(13): 1658 - 1676. [Abstract] [Full Text]

T. Quan and G. J. Fisher Cloning and Characterization of the Human Protein Kinase C-eta Promoter J. Biol. Chem., October 1, 1999; 274(40): 28566 - 28574. [Abstract] [Full Text] [PDF]

J. F. Brown, Q. Chang, B. D. Soper, and B. L. Tepperman Protein kinase C mediates experimental colitis in the rat Am J Physiol Gastrointest Liver Physiol, March 1, 1999; 276(3): G583 590. [Abstract] [Full Text] [PDF]

S. A. Matthews, E. Rozengurt, and D. Cantrell Characterization of Serine 916 as an in Vivo Autophosphorylation Site for Protein Kinase D/Protein Kinase C{micro} J. Biol. Chem., September 10, 1999; 274(37): 26543 - 26549. [Abstract] [Full Text] [PDF]

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N. Dzimiri Regulation of beta -Adrenoceptor Signaling in Cardiac Function and Disease Pharmacol. Rev., September 1, 1999; 51(3): 465 - 502. [Abstract] [Full Text] [PDF]

L. L. Hansen, Y. Ikeda, G. S. Olsen, A. K. Busch, and L. Mosthaf Insulin Signaling Is Inhibited by Micromolar Concentrations of H2O2. EVIDENCE FOR A ROLE OF H2O2 IN TUMOR NECROSIS FACTOR alpha -MEDIATED INSULIN RESISTANCE J. Biol. Chem., August 27, 1999; 274(35): 25078 - 25084. [Abstract] [Full Text] [PDF]

M. Segura, J. Stankova, and M. Gottschalk Heat-Killed Streptococcus suis Capsular Type 2 Strains Stimulate Tumor Necrosis Factor Alpha and Interleukin-6 Production by Murine Macrophages Infect. Immun., September 1, 1999; 67(9): 4646 - 4654. [Abstract] [Full Text] [PDF]

M. Medkova and W. Cho Interplay of C1 and C2 Domains of Protein Kinase C-alpha in Its Membrane Binding and Activation J. Biol. Chem., July 9, 1999; 274(28): 19852 - 19861. [Abstract] [Full Text] [PDF]

S. J. Coultrap, H. Sun, T. E. Tenner Jr., and T. K. Machu Competitive Antagonism of the Mouse 5-Hydroxytryptamine3 Receptor by Bisindolylmaleimide I, a "Selective" Protein Kinase C Inhibitor J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 76 - 82. [Abstract] [Full Text]

D. Strassheim, L. G. May, K. A. Varker, H. L. Puhl, S. H. Phelps, R. A. Porter, R. S. Aronstam, J. D. Noti, and C. L. Williams M3 Muscarinic Acetylcholine Receptors Regulate Cytoplasmic Myosin by a Process Involving RhoA and Requiring Conventional Protein Kinase C Isoforms J. Biol. Chem., June 25, 1999; 274(26): 18675 - 18685. [Abstract] [Full Text] [PDF]

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T. Pawelczyk and A. Matecki Phospholipase C-{delta}3 binds with high specificity to phosphatidylinositol 4,5-bisphosphate and phosphatidic acid in bilayer membranes Eur. J. Biochem., June 1, 1999; 262(2): 291 - 298. [Abstract] [Full Text]

R. Zeidman, B. Löfgren, S. Påhlman, and C. Larsson PKCepsilon , Via its Regulatory Domain and Independently of its Catalytic Domain, Induces Neurite-like Processes in Neuroblastoma Cells J. Cell Biol., May 17, 1999; 145(4): 713 - 726. [Abstract] [Full Text]

A. Virkamäki, K. Ueki, and C. R. Kahn Protein–protein interaction in insulin signaling and the molecular mechanisms of insulin resistance J. Clin. Invest., April 1, 1999; 103(7): 931 - 943. [Full Text]

R. T. Waldron, T. Iglesias, and E. Rozengurt The Pleckstrin Homology Domain of Protein Kinase D Interacts Preferentially with the eta Isoform of Protein Kinase C J. Biol. Chem., April 2, 1999; 274(14): 9224 - 9230. [Abstract] [Full Text] [PDF]

L. Q. Dong, R.-b. Zhang, P. Langlais, H. He, M. Clark, L. Zhu, and F. Liu Primary Structure, Tissue Distribution, and Expression of Mouse Phosphoinositide-dependent Protein Kinase-1, a Protein Kinase That Phosphorylates and Activates Protein Kinase Czeta J. Biol. Chem., March 19, 1999; 274(12): 8117 - 8122. [Abstract] [Full Text] [PDF]

D. C. GADSBY and A. C. NAIRN Control of CFTR Channel Gating by Phosphorylation and Nucleotide Hydrolysis Physiol Rev, January 1, 1999; 79(1): 77 - 107. [Abstract] [Full Text]

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V. Micol, P. Sánchez-Piñera, J. Villalaín, A. de Godos, and J. C. GómezFernández Correlation between Protein Kinase C alpha Activity and Membrane Phase Behavior Biophys. J., February 1, 1999; 76(2): 916 - 927. [Abstract] [Full Text]

G. Brooks and D. J. Hearse Role of Protein Kinase C in Ischemic Preconditioning: Player or Spectator? Circ. Res., September 1, 1996; 79(3): 628 - 631. [Full Text]

J.-W. Soh, E. H. Lee, R. Prywes, and I. B. Weinstein Novel Roles of Specific Isoforms of Protein Kinase C in Activation of the c-fos Serum Response Element Mol. Cell. Biol., February 1, 1999; 19(2): 1313 - 1324. [Abstract] [Full Text] [PDF]

R. A. McKay, L. J. Miraglia, L. L. Cummins, S. R. Owens, H. Sasmor, and N. M. Dean Characterization of a Potent and Specific Class of Antisense Oligonucleotide Inhibitor of Human Protein Kinase C-alpha Expression J. Biol. Chem., January 15, 1999; 274(3): 1715 - 1722. [Abstract] [Full Text] [PDF]

Y. Ishikawa and C. J. Homcy The Adenylyl Cyclases as Integrators of Transmembrane Signal Transduction Circ. Res., March 1, 1997; 80(3): 297 - 304. [Full Text]

W. Tsai, A. D. Morielli, T. G. Cachero, and E. G. Peralta Receptor protein tyrosine phosphatase alpha participates in the m1 muscarinic acetylcholine receptor-dependent regulation of Kv1.2 channel activity EMBO J., January 4, 1999; 18(1): 109 - 118. [Abstract] [Full Text]

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K. C. Das, X.-l. Guo, and C. W. White Protein Kinase Cdelta -dependent Induction of Manganese Superoxide Dismutase Gene Expression by Microtubule-active Anticancer Drugs J. Biol. Chem., December 18, 1998; 273(51): 34639 - 34645. [Abstract] [Full Text] [PDF]

S. Kawamura, K.-I. Yoshida, T. Miura, Y. Mizukami, and M. Matsuzaki Ischemic preconditioning translocates PKC-delta and -epsilon , which mediate functional protection in isolated rat heart Am J Physiol Heart Circ Physiol, December 1, 1998; 275(6): H2266 2271. [Abstract] [Full Text]

O. Cachia, J. E. Benna, E. Pedruzzi, B. Descomps, M.-A. GougerotPocidalo, and C.-L. Leger alpha -Tocopherol Inhibits the Respiratory Burst in Human Monocytes. ATTENUATION OF p47phox MEMBRANE TRANSLOCATION AND PHOSPHORYLATION J. Biol. Chem., December 4, 1998; 273(49): 32801 - 32805. [Abstract] [Full Text] [PDF]

C. Brodie, K. Bogi, P. Acs, P. S. Lorenzo, L. Baskin, and P. M. Blumberg Protein Kinase C delta (PKCdelta ) Inhibits the Expression of Glutamine Synthetase in Glial Cells via the PKCdelta Regulatory Domain and Its Tyrosine Phosphorylation J. Biol. Chem., November 13, 1998; 273(46): 30713 - 30718. [Abstract] [Full Text] [PDF]

M. F. Denning, Y. Wang, B. J. Nickoloff, and T. Wrone-Smith Protein Kinase Cdelta Is Activated by Caspase-dependent Proteolysis during Ultraviolet Radiation-induced Apoptosis of Human Keratinocytes J. Biol. Chem., November 6, 1998; 273(45): 29995 - 30002. [Abstract] [Full Text] [PDF]

H. Kawasaki, G. M. Springett, S. Toki, J. J. Canales, P. Harlan, J. P. Blumenstiel, E. J. Chen, I. A. Bany, N. Mochizuki, A. Ashbacher, M. Matsuda, D. E. Housman, and A. M. Graybiel A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia PNAS, October 27, 1998; 95(22): 13278 - 13283.

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[Abstract] [Full Text] [PDF]

T. Iglesias, R. T. Waldron, and E. Rozengurt Identification of in Vivo Phosphorylation Sites Required for Protein Kinase D Activation J. Biol. Chem., October 16, 1998; 273(42): 27662 - 27667. [Abstract] [Full Text] [PDF]

J. Zhao, O. Renner, L. Wightman, P. H. Sugden, L. Stewart, A. D. Miller, D. S. Latchman, and M. S. Marber The Expression of Constitutively Active Isotypes of Protein Kinase C to Investigate Preconditioning J. Biol. Chem., September 4, 1998; 273(36): 23072 - 23079. [Abstract] [Full Text] [PDF]

S. J. Slater, F. J. Taddeo, A. Mazurek, B. A. Stagliano, S. K. Milano, M. B. Kelly, C. Ho, and C. D. Stubbs Inhibition of Membrane Lipid-independent Protein Kinase Calpha Activity by Phorbol Esters, Diacylglycerols, and Bryostatin-1 J. Biol. Chem., September 4, 1998; 273(36): 23160 - 23168. [Abstract] [Full Text] [PDF]

E. M. Smyth, W. H. Li, and G. A. FitzGerald Phosphorylation of the Prostacyclin Receptor during Homologous Desensitization. A CRITICAL ROLE FOR PROTEIN KINASE C J. Biol. Chem., September 4, 1998; 273(36): 23258 - 23266. [Abstract] [Full Text] [PDF]

J.-H. Chang, J. C. Pratt, S. Sawasdikosol, R. Kapeller, and S. J. Burakoff The Small GTP-Binding Protein Rho Potentiates AP-1 Transcription in T Cells Mol. Cell. Biol., September 1, 1998; 18(9): 4986 - 4993. [Abstract] [Full Text]

Y. Gokmen-Polar and A. P. Fields Mapping of a Molecular Determinant for Protein Kinase C beta II Isozyme Function J. Biol. Chem., August 7, 1998; 273(32): 20261 - 20266. [Abstract] [Full Text] [PDF]

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S. K. Lee, W. G. Qing, W. Mar, L. Luyengi, R. G. Mehta, K. Kawanishi, H. H. S. Fong, C. W. W. Beecher, A. D. Kinghorn, and J. M. Pezzuto Angoline and Chelerythrine, Benzophenanthridine Alkaloids That Do Not Inhibit Protein Kinase C J. Biol. Chem., July 31, 1998; 273(31): 19829 - 19833. [Abstract] [Full Text] [PDF]

A. M. Pepio, X. Fan, and W. S. Sossin The Role of C2 Domains in Ca2+-activated and Ca2+-independent Protein Kinase Cs in Aplysia J. Biol. Chem., July 24, 1998; 273(30): 19040 - 19048. [Abstract] [Full Text] [PDF]

M. Medkova and W. Cho Mutagenesis of the C2 Domain of Protein Kinase C-alpha . DIFFERENTIAL ROLES OF Ca2+ LIGANDS AND MEMBRANE BINDING RESIDUES J. Biol. Chem., July 10, 1998; 273(28): 17544 - 17552. [Abstract] [Full Text] [PDF]

T. E. Smithgall Signal Transduction Pathways Regulating Hematopoietic Differentiation Pharmacol. Rev., March 1, 1998; 50(1): 1 - 20. [Abstract] [Full Text] [PDF]

H.-Y. Lin, P. M. Yen, F. B. Davis, and P. J. Davis Protein synthesis-dependent potentiation by thyroxine of antiviral activity of interferon-gamma Am J Physiol Cell Physiol, October 1, 1997; 273(4): C1225 - 1232. [Abstract] [Full Text]

P. B. Dennis, N. Pullen, R. B. Pearson, S. C. Kozma, and G. Thomas Phosphorylation Sites in the Autoinhibitory Domain Participate in p70s6k Activation Loop Phosphorylation J. Biol. Chem., June 12, 1998; 273(24): 14845 - 14852. [Abstract] [Full Text] [PDF]

W. Qi, E. Loh, G. Vilaire, and J. S. Bennett

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Regulation of alpha IIbbeta 3 Function in Human B Lymphocytes J. Biol. Chem., June 12, 1998; 273(24): 15271 - 15278. [Abstract] [Full Text] [PDF]

E. Gozal, A. L. Roussel, G. A. Holt, L. Gozal, Y. M. Gozal, J. E. Torres, and D. Gozal Protein kinase C modulation of ventilatory response to hypoxia in nucleus tractus solitarii of conscious rats J Appl Physiol, June 1, 1998; 84(6): 1982 - 1990. [Abstract] [Full Text]

C. Mineo, Y.-S. Ying, C. Chapline, S. Jaken, and R. G.W. Anderson Targeting of Protein Kinase Calpha to Caveolae J. Cell Biol., April 20, 1998; 141(3): 601 - 610. [Abstract] [Full Text]

X. Feng, J. Zhang, L. S. Barak, T. Meyer, M. G. Caron, and Y. A. Hannun Visualization of Dynamic Trafficking of a Protein Kinase C beta II/Green Fluorescent Protein Conjugate Reveals Differences in G Protein-coupled Receptor Activation and Desensitization J. Biol. Chem., April 24, 1998; 273(17): 10755 - 10762. [Abstract] [Full Text] [PDF]

M. L. Dell'Acqua, M. C. Faux, J. Thorburn, A. Thorburn, and J. D. Scott Membrane-targeting sequences on AKAP79 bind phosphatidylinositol-4,5-bisphosphate EMBO J., April 15, 1998; 17(8): 2246 - 2260. [Abstract] [Full Text] [PDF]

T. J. Searl and E. M. Silinsky Increases in Acetylcholine Release Produced by Phorbol Esters Are Not Mediated by Protein Kinase C at Motor Nerve Endings J. Pharmacol. Exp. Ther., April 1, 1998; 285(1): 247 - 251. [Abstract] [Full Text]

D. G. Watson, J. M. Watterson, and R. H. Lenox Sodium Valproate Down-regulates the Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) in Immortalized Hippocampal Cells: A Property of Protein Kinase C-Mediated Mood Stabilizers

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J. Pharmacol. Exp. Ther., April 1, 1998; 285(1): 307 - 316. [Abstract] [Full Text]

A. M. Parissenti, A. F. Kirwan, S. A. Kim, C. M. Colantonio, and B. P. Schimmer Inhibitory Properties of the Regulatory Domains of Human Protein Kinase Calpha and Mouse Protein Kinase Cepsilon J. Biol. Chem., April 10, 1998; 273(15): 8940 - 8945. [Abstract] [Full Text] [PDF]

M. Levy, J. Jing, D. Chikvashvili, W. B. Thornhill, and I. Lotan Activation of a Metabotropic Glutamate Receptor and Protein Kinase C Reduce the Extent of Inactivation of the K+ Channel Kv1.1/Kvbeta 1.1 via Dephosphorylation of Kv1.1 J. Biol. Chem., March 13, 1998; 273(11): 6495 - 6502. [Abstract] [Full Text] [PDF]

M. J. Savage, S. P. Trusko, D. S. Howland, L. R. Pinsker, S. Mistretta, A. G. Reaume, B. D. Greenberg, R. Siman, and R. W. Scott J. Neurosci., March 1, 1998; 18(5): 1743 - 1752. [Abstract] [Full Text]

D. Koya, M. R. Jirousek, Y.-W. Lin, H. Ishii, K. Kuboki, and G. L. King Characterization of Protein Kinase C beta Isoform Activation on the Gene Expression of Transforming Growth Factor-beta , Extracellular Matrix Components, and Prostanoids in the Glomeruli of Diabetic Rats J. Clin. Invest., July 1, 1997; 100(1): 115 - 126. [Abstract] [Full Text]

S. Nowicki, S. L. Chen, O. Aizman, X. J. Cheng, D. Li, C. Nowicki, A. Nairn, P. Greengard, and A. Aperia 20-Hydroxyeicosa-Tetraenoic Acid (20 HETE) Activates Protein Kinase C . Role in Regulation of Rat Renal Na+,K+-ATPase J. Clin. Invest., March 15, 1997; 99(6): 1224 - 1230. [Abstract] [Full Text]

F. Bornancin and P. J. Parker Phosphorylation of Protein Kinase C-alpha on Serine 657Controls the Accumulation of Active Enzyme and Contributes to Its

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Phosphatase-resistant State J. Biol. Chem., February 7, 1997; 272(6): 3544 - 3549. [Abstract] [Full Text] [PDF]

Y. Jia, C. J. Mathews, and J. W. Hanrahan Phosphorylation by Protein Kinase C Is Required For Acute Activation of Cystic Fibrosis Transmembrane Conductance Regulator by Protein Kinase A J. Biol. Chem., February 21, 1997; 272(8): 4978 - 4984. [Abstract] [Full Text] [PDF]

S. A. Rotenberg and X.-g. Sun Photoinduced Inactivation of Protein Kinase C by Dequalinium Identifies the RACK-1-binding Domain as a Recognition Site J. Biol. Chem., January 23, 1998; 273(4): 2390 - 2395. [Abstract] [Full Text] [PDF]

L. Bloom and H. R. Horvitz The Caenorhabditis elegans gene unc-76 and its human homologs define a new gene family involved in axonal outgrowth and fasciculation PNAS, April 1, 1997; 94(7): 3414 - 3419. [Abstract] [Full Text] [PDF]

D.-F. Liao, B. Monia, N. Dean, and B. C. Berk Protein Kinase C-zeta Mediates Angiotensin II Activation of ERK1/2 in Vascular Smooth Muscle Cells J. Biol. Chem., March 7, 1997; 272(10): 6146 - 6150. [Abstract] [Full Text] [PDF]

S. J. Slater, M. B. Kelly, J. D. Larkin, C. Ho, A. Mazurek, F. J. Taddeo, M. D. Yeager, and C. D. Stubbs Interaction of Alcohols and Anesthetics with Protein Kinase Calpha J. Biol. Chem., March 7, 1997; 272(10): 6167 - 6173. [Abstract] [Full Text] [PDF]

A. Islas-Trejo, M. Land, I. Tcherepanova, J. H. Freedman, and C. S. Rubin Structure and Expression of the Caenorhabditis elegans Protein

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Kinase C2 Gene. ORIGINS AND REGULATED EXPRESSION OF A FAMILY OF Ca2+-ACTIVATED PROTEIN KINASE C ISOFORMS J. Biol. Chem., March 7, 1997; 272(10): 6629 - 6640. [Abstract] [Full Text] [PDF]

E. O. Harrington, J. Loffler, P. R. Nelson, K. C. Kent, M. Simons, and J. A. Ware Enhancement of Migration by Protein Kinase Calpha and Inhibition of Proliferation and Cell Cycle Progression by Protein Kinase Cdelta in Capillary Endothelial Cells J. Biol. Chem., March 14, 1997; 272(11): 7390 - 7397. [Abstract] [Full Text] [PDF]

I. P. Udovichenko, A. C. Newton, and D. S. Williams Contribution of Protein Kinase C to the Phosphorylation of Rhodopsin in Intact Retinas J. Biol. Chem., March 21, 1997; 272(12): 7952 - 7959. [Abstract] [Full Text] [PDF]

J. Sloan-Lancaster, W. Zhang, J. Presley, B. L. Williams, R. T. Abraham, J. Lippincott-Schwartz, and L. E. Samelson Regulation of ZAP-70 Intracellular Localization: Visualization with the Green Fluorescent Protein J. Exp. Med., November 17, 1997; 186(10): 1713 - 1724. [Abstract] [Full Text]

J. V. Gray, J. P. Ogas, Y. Kamada, M. Stone, D. E. Levin, and I. Herskowitz A role for the Pkc1 MAP kinase pathway of Saccharomyces cerevisiae in bud emergence and identification of a putative upstream regulator EMBO J., August 15, 1997; 16(16): 4924 - 4937. [Abstract] [Full Text]

R. J.H. Wojcikiewicz and J. A. Oberdorf Degradation of Inositol 1,4,5-Trisphosphate Receptors during Cell Stimulation Is a Specific Process Mediated by Cysteine Protease Activity J. Biol. Chem., July 12, 1996; 271(28): 16652 - 16655. [Abstract] [Full Text] [PDF]

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Z. Szallasi, K. Bogi, S. Gohari, T. Biro, P. Acs, and P. M. Blumberg Non-equivalent Roles for the First and Second Zinc Fingers of Protein Kinase Cdelta . EFFECT OF THEIR MUTATION ON PHORBOL ESTER-INDUCED TRANSLOCATION IN NIH 3T3 CELLS J. Biol. Chem., August 2, 1996; 271(31): 18299 - 18301. [Abstract] [Full Text] [PDF]

H.-W. Lee, L. Smith, G. R. Pettit, A. Vinitsky, and J. B. Smith Ubiquitination of Protein Kinase C-alpha and Degradation by the Proteasome J. Biol. Chem., August 30, 1996; 271(35): 20973 - 20976. [Abstract] [Full Text] [PDF]

T. Chatila, K. A. Anderson, N. Ho, and A. R. Means A Unique Phosphorylation-dependent Mechanism for the Activation of Ca2+/Calmodulin-dependent Protein Kinase Type IV/GR J. Biol. Chem., August 30, 1996; 271(35): 21542 - 21548. [Abstract] [Full Text] [PDF]

S. K. DebBurman, J. Ptasienski, J. L. Benovic, and M. M. Hosey G Protein-coupled Receptor Kinase GRK2 Is a Phospholipiddependent Enzyme That Can Be Conditionally Activated by G Protein beta gamma Subunits J. Biol. Chem., September 13, 1996; 271(37): 22552 - 22562. [Abstract] [Full Text] [PDF]

N. E. Ward, K. R. Gravitt, and C. A. O'Brian Covalent Modification of Protein Kinase C Isozymes by the Inactivating Peptide Substrate Analog N-Biotinyl-Arg-Arg-ArgCys-Leu-Arg-Arg-Leu. EVIDENCE THAT THE BIOTINYLATED PEPTIDE IS AN ACTIVE-SITE AFFINITY LABEL J. Biol. Chem., September 27, 1996; 271(39): 24193 - 24200. [Abstract] [Full Text] [PDF]

J. A. Johnson, M. O. Gray, C.-H. Chen, and D. Mochly-Rosen A Protein Kinase C Translocation Inhibitor as an Isozymeselective Antagonist of Cardiac Function J. Biol. Chem., October 4, 1996; 271(40): 24962 - 24966. [Abstract] [Full Text] [PDF]

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M. Glaser, S. Wanaski, C. A. Buser, V. Boguslavsky, W. Rashidzada, A. Morris, M. Rebecchi, S. F. Scarlata, L. W. Runnels, G. D. Prestwich, J. Chen, A. Aderem, J. Ahn, and S. McLaughlin Myristoylated Alanine-rich C Kinase Substrate (MARCKS) Produces Reversible Inhibition of Phospholipase C by Sequestering Phosphatidylinositol 4,5-Bisphosphate in Lateral Domains J. Biol. Chem., October 18, 1996; 271(42): 26187 - 26193. [Abstract] [Full Text] [PDF]

J. Beltman, F. McCormick, and S. J. Cook The Selective Protein Kinase C Inhibitor, Ro-31-8220, Inhibits Mitogen-activated Protein Kinase Phosphatase-1 (MKP-1) Expression, Induces c-Jun Expression, and Activates Jun Nterminal Kinase J. Biol. Chem., October 25, 1996; 271(43): 27018 - 27024. [Abstract] [Full Text] [PDF]

W.-W. Tchou, W. N. Rom, and K.-M. Tchou-Wong Novel Form of p21WAF1/CIP1/SDI1 Protein in Phorbol Esterinduced G2/M Arrest J. Biol. Chem., November 22, 1996; 271(47): 29556 - 29560. [Abstract] [Full Text] [PDF]

C. Huang, W.-y. Ma, G. T. Bowden, and Z. Dong Ultraviolet B-induced Activated Protein-1 Activation Does Not Require Epidermal Growth Factor Receptor but Is Blocked by a Dominant Negative PKClambda /iota J. Biol. Chem., December 6, 1996; 271(49): 31262 - 31268. [Abstract] [Full Text] [PDF]

B. Peng, N. A. Morrice, L. C. Groenen, and R. E.H. Wettenhall Phosphorylation Events Associated with Different States of Activation of a Hepatic Cardiolipin/Protease-activated Protein Kinase. STRUCTURAL IDENTITY TO THE PROTEIN KINASE N-TYPE PROTEIN KINASES J. Biol. Chem., December 13, 1996; 271(50): 32233 - 32240. [Abstract] [Full Text] [PDF]

G. Hansra, F. Bornancin, R. Whelan, B. A. Hemmings, and P. J. Parker 12-O-Tetradecanoylphorbol-13-acetate-induced Dephosphorylation of Protein Kinase Calpha Correlates with the

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Presence of a Membrane-associated Protein Phosphatase 2A Heterotrimer J. Biol. Chem., December 20, 1996; 271(51): 32785 - 32788. [Abstract] [Full Text] [PDF]

W. Yu, J. Liu, N. A. Morrice, and R. E.H. Wettenhall Isolation and Characterization of a Structural Homologue of Human PRK2 from Rat Liver. DISTINGUISHING SUBSTRATE AND LIPID ACTIVATOR SPECIFICITIES J. Biol. Chem., April 11, 1997; 272(15): 10030 - 10034. [Abstract] [Full Text] [PDF]

N. M. Greene, D. S. Williams, and A. C. Newton Identification of Protein Kinase C Phosphorylation Sites on Bovine Rhodopsin J. Biol. Chem., April 18, 1997; 272(16): 10341 - 10344. [Abstract] [Full Text] [PDF]

D. Hiregowdara, H. Avraham, Y. Fu, R. London, and S. Avraham Tyrosine Phosphorylation of the Related Adhesion Focal Tyrosine Kinase in Megakaryocytes upon Stem Cell Factor and Phorbol Myristate Acetate Stimulation and Its Association with Paxillin J. Biol. Chem., April 18, 1997; 272(16): 10804 - 10810. [Abstract] [Full Text] [PDF]

L. V. Dekker and P. J. Parker Regulated Binding of the Protein Kinase C Substrate GAP-43 to the V0/C2 Region of Protein Kinase C-delta J. Biol. Chem., May 9, 1997; 272(19): 12747 - 12753. [Abstract] [Full Text] [PDF]

D. Harris, N. Reiss, and Z. Naor Differential Activation of Protein Kinase C delta and epsilon Gene Expression by Gonadotropin-releasing Hormone in alpha T3-1 Cells. AUTOREGULATION BY PROTEIN KINASE C J. Biol. Chem., May 23, 1997; 272(21): 13534 - 13540. [Abstract] [Full Text] [PDF]

D. Rosson, T. G. O'Brien, J. A. Kampherstein, Z. Szallasi, K. Bogi, P. M. Blumberg, and J. M. Mullin

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Protein Kinase C-alpha Activity Modulates Transepithelial Permeability and Cell Junctions in the LLC-PK1 Epithelial Cell Line J. Biol. Chem., June 6, 1997; 272(23): 14950 - 14953. [Abstract] [Full Text] [PDF]

S. Orita, A. Naito, G. Sakaguchi, M. Maeda, H. Igarashi, T. Sasaki, and Y. Takai Physical and Functional Interactions of Doc2 and Munc13 in Ca2+-dependent Exocytotic Machinery J. Biol. Chem., June 27, 1997; 272(26): 16081 - 16084. [Abstract] [Full Text] [PDF]

P. Herrera-Velit, K. L. Knutson, and N. E. Reiner Phosphatidylinositol 3-Kinase-dependent Activation of Protein Kinase C-zeta in Bacterial Lipopolysaccharide-treated Human Monocytes J. Biol. Chem., June 27, 1997; 272(26): 16445 - 16452. [Abstract] [Full Text] [PDF]

M. C. Faux and J. D. Scott Regulation of the AKAP79-Protein Kinase C Interaction by Ca2+/Calmodulin J. Biol. Chem., July 4, 1997; 272(27): 17038 - 17044. [Abstract] [Full Text] [PDF]

A. S. Edwards and A. C. Newton Phosphorylation at Conserved Carboxyl-terminal Hydrophobic Motif Regulates the Catalytic and Regulatory Domains of Protein Kinase C J. Biol. Chem., July 18, 1997; 272(29): 18382 - 18390. [Abstract] [Full Text] [PDF]

R. Minakami, N. Jinnai, and H. Sugiyama Phosphorylation and Calmodulin Binding of the Metabotropic Glutamate Receptor Subtype 5 (mGluR5) Are Antagonistic in Vitro J. Biol. Chem., August 8, 1997; 272(32): 20291 - 20298. [Abstract] [Full Text] [PDF]

P. Acs, K. Bogi, P. S. Lorenzo, A. M. Marquez, T. Biro, Z. Szallasi, and P. M. Blumberg

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The Catalytic Domain of Protein Kinase C Chimeras Modulates the Affinity and Targeting of Phorbol Ester-induced Translocation J. Biol. Chem., August 29, 1997; 272(35): 22148 - 22153. [Abstract] [Full Text] [PDF]

M. G. Newlon, M. Roy, Z. E. Hausken, J. D. Scott, and P. A. Jennings The A-kinase Anchoring Domain of Type IIalpha cAMP-dependent Protein Kinase Is Highly Helical J. Biol. Chem., September 19, 1997; 272(38): 23637 - 23644. [Abstract] [Full Text] [PDF]

M. J. Caloca, N. Fernandez, N. E. Lewin, D. Ching, R. Modali, P. M. Blumberg, and M. G. Kazanietz beta 2-Chimaerin Is a High Affinity Receptor for the Phorbol Ester Tumor Promoters J. Biol. Chem., October 17, 1997; 272(42): 26488 - 26496. [Abstract] [Full Text] [PDF]

A. Arbuzova, J. Wang, D. Murray, J. Jacob, D. S. Cafiso, and S. McLaughlin Kinetics of Interaction of the Myristoylated Alanine-rich C Kinase Substrate, Membranes, and Calmodulin J. Biol. Chem., October 24, 1997; 272(43): 27167 - 27177. [Abstract] [Full Text] [PDF]

S. Tang, K. G. Morgan, C. Parker, and J. A. Ware Requirement for Protein Kinase C theta for Cell Cycle Progression and Formation of Actin Stress Fibers and Filopodia in Vascular Endothelial Cells J. Biol. Chem., November 7, 1997; 272(45): 28704 - 28711. [Abstract] [Full Text] [PDF]

P. Acs, Q. J. Wang, K. Bogi, A. M. Marquez, P. S. Lorenzo, T. Biro, Z. Szallasi, J. F. Mushinski, and P. M. Blumberg Both the Catalytic and Regulatory Domains of Protein Kinase C Chimeras Modulate the Proliferative Properties of NIH 3T3 Cells J. Biol. Chem., November 7, 1997; 272(45): 28793 - 28799. [Abstract] [Full Text] [PDF]

O. Traub, B. P. Monia, N. M. Dean, and B. C. Berk

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PKC-epsilon Is Required for Mechano-sensitive Activation of ERK1/2 in Endothelial Cells J. Biol. Chem., December 12, 1997; 272(50): 31251 - 31257. [Abstract] [Full Text] [PDF]

P. S. Lorenzo, K. Bogi, P. Acs, G. R. Pettit, and P. M. Blumberg The Catalytic Domain of Protein Kinase Cdelta Confers Protection from Down-regulation Induced by Bryostatin 1 J. Biol. Chem., December 26, 1997; 272(52): 33338 - 33343. [Abstract] [Full Text] [PDF]

N. Oka, M. Yamamoto, C. Schwencke, J.-i. Kawabe, T. Ebina, S. Ohno, J. Couet, M. P. Lisanti, and Y. Ishikawa Caveolin Interaction with Protein Kinase C. ISOENZYMEDEPENDENT REGULATION OF KINASE ACTIVITY BY THE CAVEOLIN SCAFFOLDING DOMAIN PEPTIDE J. Biol. Chem., December 26, 1997; 272(52): 33416 - 33421. [Abstract] [Full Text] [PDF]

L. Hilgenberg, S. Yearwood, S. Milstein, and K. Miles Neural Influence on Protein Kinase C Isoform Expression in Skeletal Muscle J. Neurosci., August 15, 1996; 16(16): 4994 - 5003. [Abstract] [Full Text]

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