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1 Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, and 6 Department of Basic Science and Oral Research, School of Dentistry, University of Colorado Health Sciences Center, Denver 80262; 2 Denver Veterans Affairs Medical Center, Denver, Colorado 80220; 3 Department of Pharmacology, University of California, San Diego, La Jolla 92093; 4 Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford 94305; 7 Department of Neurology, Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, California 94608; and 5 Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555
Individual protein kinase C (PKC) isozymes have been implicated in many cellular responses important in lung health and disease, including permeability, contraction, migration, hypertrophy, proliferation, apoptosis, and secretion. New ideas on mechanisms that regulate PKC activity, including the identification of a novel PKC kinase, 3-phosphoinositide-dependent kinase-1 (PDK-1), that regulates phosphorylation of PKC, have been advanced. The importance of targeted translocation of PKC and isozyme-specific binding proteins (like receptors for activated C-kinase and caveolins) is well established. Phosphorylation state and localization are now thought to be key determinants of isozyme activity and specificity. New concepts on the role of individual PKC isozymes in proliferation and apoptosis are emerging. Opposing roles for selected isozymes in the same cell system have been defined. Coupling to the Wnt signaling pathway has been described. Phenotypes for PKC knockout mice have recently been reported. More specific approaches for studying PKC isozymes and their role in cell responses have been developed. Strengths and weaknesses of different experimental strategies are reviewed. Future directions for investigation are identified.
pulmonary disease; proliferation; apoptosis; 3-phosphoinositide-dependent kinase-1; receptor for activated C-kinase; transgenic mice
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 G. N. Pandey, Y. Dwivedi, H. S. Rizavi, X. Ren, and R. R. Conley Decreased Catalytic Activity and Expression of Protein Kinase C Isozymes in Teenage Suicide Victims: A Postmortem Brain Study Arch Gen Psychiatry, July 1, 2004; 61(7): 685 - 693. [Abstract] [Full Text] [PDF]
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 X. Liu, M. L. Godwin, and G. Nowak Protein kinase C-{alpha} inhibits the repair of oxidative phosphorylation after S-(1,2-dichlorovinyl)-L-cysteine injury in renal cells Am J Physiol Renal Physiol, July 1, 2004; 287(1): F64 - F73. [Abstract] [Full Text] [PDF]
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V. U. Rao, H. Shiraishi, and P. J. McDermott PKC-{epsilon} regulation of extracellular signal-regulated kinase: a potential role in phenylephrine-induced cardiocyte growth Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2195 - H2203. [Abstract] [Full Text] [PDF]
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N. Kedei, D. J. Lundberg, A. Toth, P. Welburn, S. H. Garfield, and P. M. Blumberg Characterization of the Interaction of Ingenol 3-Angelate with Protein Kinase C Cancer Res., May 1, 2004; 64(9): 3243 - 3255. [Abstract] [Full Text] [PDF]
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 D. Brehmer, K. Godl, B. Zech, J. Wissing, and H. Daub Proteome-wide Identification of Cellular Targets Affected by Bisindolylmaleimide-type Protein Kinase C Inhibitors Mol. Cell. Proteomics, May 1, 2004; 3(5): 490 - 500. [Abstract] [Full Text] [PDF]
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V. O. Rybin, J. Guo, A. Sabri, H. Elouardighi, E. Schaefer, and S. F. Steinberg Stimulus-specific Differences in Protein Kinase C{delta} Localization and Activation Mechanisms in Cardiomyocytes J. Biol. Chem., April 30, 2004; 279(18): 19350 - 19361. [Abstract] [Full Text] [PDF]
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A. SPAT and L. HUNYADY Control of Aldosterone Secretion: A Model for Convergence in Cellular Signaling Pathways Physiol Rev, April 1, 2004; 84(2): 489 - 539. [Abstract] [Full Text] [PDF]
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G. Nowak, D. Bakajsova, and G. L. Clifton Protein kinase C-{epsilon} modulates mitochondrial function and active Na+ transport after oxidant injury in renal cells Am J Physiol Renal Physiol, February 1, 2004; 286(2): F307 - F316. [Abstract] [Full Text] [PDF]
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L. Sun, G. Mao, and A. K. Rao Association of CBFA2 mutation with decreased platelet PKC-{theta} and impaired receptor-mediated activation of GPIIb-IIIa and pleckstrin phosphorylation: proteins regulated by CBFA2 play a role in GPIIb-IIIa activation Blood, February 1, 2004; 103(3): 948 - 954. [Abstract] [Full Text] [PDF]
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P. J. Parker and J. Murray-Rust PKC at a glance J. Cell Sci., January 15, 2004; 117(2): 131 - 132. [Full Text] [PDF]
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J.-M. Wu, L. Xiao, X.-K. Cheng, L.-X. Cui, N.-H. Wu, and Y.-F. Shen PKC{epsilon} Is a Unique Regulator for hsp90{beta} Gene in Heat Shock Response J. Biol. Chem., December 19, 2003; 278(51): 51143 - 51149. [Abstract] [Full Text] [PDF]
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Y. Jossin, M. Ogawa, C. Metin, F. Tissir, and A. M. Goffinet Inhibition of Src Family Kinases and Non-Classical Protein Kinases C Induce a Reeler-Like Malformation of Cortical Plate Development J. Neurosci., October 29, 2003; 23(30): 9953 - 9959. [Abstract] [Full Text] [PDF]
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H. Lenasi, K. Kohlstedt, B. Fichtlscherer, A. Mulsch, R. Busse, and I. Fleming Amlodipine activates the endothelial nitric oxide synthase by altering phosphorylation on Ser1177 and Thr495 Cardiovasc Res, October 1, 2003; 59(4): 844 - 853. [Abstract] [Full Text] [PDF]
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R. C. Y. Choi, N. L. Siow, A. W. M. Cheng, K. K. Y. Ling, E. K. K. Tung, J. Simon, E. A. Barnard, and K. W. K. Tsim ATP Acts via P2Y1 Receptors to Stimulate Acetylcholinesterase and Acetylcholine Receptor Expression: Transduction and Transcription Control J. Neurosci., June 1, 2003; 23(11): 4445 - 4456. [Abstract] [Full Text] [PDF]
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C. M. Littler, K. G. Morris Jr., K. A. Fagan, I. F. McMurtry, R. O. Messing, and E. C. Dempsey Protein kinase C-epsilon -null mice have decreased hypoxic pulmonary vasoconstriction Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1321 - H1331. [Abstract] [Full Text] [PDF]
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 B. Luo, S. M. Prescott, and M. K. Topham Association of diacylglycerol kinase {zeta} with protein kinase C {alpha}: spatial regulation of diacylglycerol signaling J. Cell Biol., March 17, 2003; 160(6): 929 - 937. [Abstract] [Full Text] [PDF]
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A. Siflinger-Birnboim and A. Johnson Protein kinase C modulates pulmonary endothelial permeability: a paradigm for acute lung injury Am J Physiol Lung Cell Mol Physiol, March 1, 2003; 284(3): L435 - L451. [Abstract] [Full Text] [PDF]
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K. Reisinger, R. Kaufmann, and J. Gille Increased Sp1 phosphorylation as a mechanism of hepatocyte growth factor (HGF/SF)-induced vascular endothelial growth factor (VEGF/VPF) transcription J. Cell Sci., January 15, 2003; 116(2): 225 - 238. [Abstract] [Full Text] [PDF]
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 M. Guo, M. H. Wu, F. Korompai, and S. Y. Yuan Upregulation of PKC genes and isozymes in cardiovascular tissues during early stages of experimental diabetes Physiol Genomics, January 15, 2003; 12(2): 139 - 146. [Abstract] [Full Text] [PDF]
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R. T. Waldron and E. Rozengurt Protein Kinase C Phosphorylates Protein Kinase D Activation Loop Ser744 and Ser748 and Releases Autoinhibition by the Pleckstrin Homology Domain J. Biol. Chem., January 3, 2003; 278(1): 154 - 163. [Abstract] [Full Text] [PDF]
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M. Nanjundan and F. Possmayer Pulmonary phosphatidic acid phosphatase and lipid phosphate phosphohydrolase Am J Physiol Lung Cell Mol Physiol, January 1, 2003; 284(1): L1 - L23. [Abstract] [Full Text] [PDF]
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E. Garcia-Garcia and C. Rosales Signal transduction during Fc receptor-mediated phagocytosis J. Leukoc. Biol., December 1, 2002; 72(6): 1092 - 1108. [Abstract] [Full Text] [PDF]
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C. B. Coyne, M. K. Vanhook, T. M. Gambling, J. L. Carson, R. C. Boucher, and L. G. Johnson Regulation of Airway Tight Junctions by Proinflammatory Cytokines Mol. Biol. Cell, September 1, 2002; 13(9): 3218 - 3234. [Abstract] [Full Text] [PDF]
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Z.-Q. Zhao and J. Vinten-Johansen Myocardial apoptosis and ischemic preconditioning Cardiovasc Res, August 15, 2002; 55(3): 438 - 455. [Abstract] [Full Text] [PDF]
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A. Zrachia, M. Dobroslav, M. Blass, G. Kazimirsky, I. Kronfeld, P. M. Blumberg, D. Kobiler, S. Lustig, and C. Brodie Infection of Glioma Cells with Sindbis Virus Induces Selective Activation and Tyrosine Phosphorylation of Protein Kinase C delta . IMPLICATIONS FOR SINDBIS VIRUS-INDUCED APOPTOSIS J. Biol. Chem., June 21, 2002; 277(26): 23693 - 23701. [Abstract] [Full Text] [PDF]
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M.-H. Disatnik, S. C. Boutet, C. H. Lee, D. Mochly-Rosen, and T. A. Rando Sequential activation of individual PKC isozymes in integrin-mediated muscle cell spreading: a role for MARCKS in an integrin signaling pathway J. Cell Sci., May 15, 2002; 115(10): 2151 - 2163. [Abstract] [Full Text] [PDF]
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S. J. Slater, J. L. Seiz, A. C. Cook, C. J. Buzas, S. A. Malinowski, J. L. Kershner, B. A. Stagliano, and C. D. Stubbs Regulation of PKCalpha Activity by C1-C2 Domain Interactions J. Biol. Chem., May 3, 2002; 277(18): 15277 - 15285. [Abstract] [Full Text] [PDF]
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B. Hendey, C. L. Zhu, and S. Greenstein Fas activation opposes PMA-stimulated changes in the localization of PKC{delta}: a mechanism for reducing neutrophil adhesion to endothelial cells J. Leukoc. Biol., May 1, 2002; 71(5): 863 - 870. [Abstract] [Full Text] [PDF]
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M. Morigi, D. Macconi, C. Zoja, R. Donadelli, S. Buelli, C. Zanchi, M. Ghilardi, and G. Remuzzi Protein Overload-Induced NF-{kappa}B Activation in Proximal Tubular Cells Requires H2O2 through a PKC-Dependent Pathway J. Am. Soc. Nephrol., May 1, 2002; 13(5): 1179 - 1189. [Abstract] [Full Text] [PDF]
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J. C. Braz, O. F. Bueno, L. J. De Windt, and J. D. Molkentin PKC{alpha} regulates the hypertrophic growth of cardiomyocytes through extracellular signal-regulated kinase1/2 (ERK1/2) J. Cell Biol., March 4, 2002; 156(5): 905 - 919. [Abstract] [Full Text] [PDF]
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