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Gene Review

PRKCA  -  protein kinase C, alpha

Homo sapiens

Synonyms: AAG6, PKC-A, PKC-alpha, PKCA, PRKACA, ...
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Disease relevance of PRKCA


Psychiatry related information on PRKCA


High impact information on PRKCA


Chemical compound and disease context of PRKCA

  • TUDCA inhibition of cholangiocarcinoma growth was blocked by BAPTA-AM, an intracellular Ca(2+) concentration ([Ca(2+)](i)) chelator, and H7, a PKC-alpha inhibitor [11].
  • Both the cytosol and membrane in C6 glioma cells express abundance of PKC alpha, delta, zeta and trace amount of PKC epsilon by Western blot analysis with isozyme-specific antibodies [12].
  • Altogether, our findings indicate that resveratrol engages PKC alpha and delta signals in gastric adenocarcinoma SNU-1 cells prior to up-regulation of antiproliferative and pro-apoptotic signals [13].
  • In contrast, C6 glioma cells treated with beta-TPA showed no growth arrest, decreased PKC-alpha protein (< 20%) and lower phosphatidylcholine synthesis [14].
  • IMPLICATIONS: 12(S)-HETE modulation of PKC alpha invasiveness may be an important mechanism of action for the regulation of the invasive potential of rat prostate carcinoma cells, and the 12-lipoxygenase enzyme and/or PKC alpha may serve as key targets for the development of anti-invasive agents useful for combating the spread of prostate cancer [15].

Biological context of PRKCA

  • MPO and PRKCA remain on the der(17) chromosome and therefore are assigned to 17(q21.3-q23.2) and 17(q22-q23.2), respectively [16].
  • The reciprocal translocation t(2;17) (q21.2; q23.2) was used to map the human genes for myeloperoxidase (MPO), protein kinase C, alpha polypeptide, PRKCA, and the anonymous DNA fragment D17S21 more precisely on human chromosome 17q [16].
  • Furthermore, TPA treatment of serum-starved NIH 3T3 cells led to phosphorylation of SEK1, and constitutively active mutants of PKC-alpha and PKC-epsilon activated the transactivation domain of c-Jun, a major substrate of JNK [17].
  • A hybrid PKC gene, PKAC, was constructed by substituting the coding region for the N-terminal 253 amino acids of PKC alpha with the N-terminal 17 amino acids of the cyclic AMP-dependent protein kinase catalytic subunit (PKA) [18].
  • The results obtained with specific inhibitors indicated that PKC-alpha pathway is necessary to mediate the estradiol-induced G1-S progression of HepG2 cells, but it does not exert any effect(s) on cyclin D(1) gene expression [19].

Anatomical context of PRKCA

  • These data are consistent with PKC alpha-dependent exocytosis of activated beta(1) integrin to the plasma membrane, where its increased surface expression mediates binding to fibronectin; conversely, catalytically active PKC alpha-driven internalization of beta(1) integrin results in MM cell de-adhesion [2].
  • Western blotting analysis established that Zellweger fibroblasts express PKC alpha, epsilon, and zeta [20].
  • RNA from six leukemic T cell lines was probed for PKC-alpha, -beta, and -gamma message before and after activation [21].
  • These results establish that modulation of the ether lipid composition of membranes can alter PKC isozyme translocation and indicate that a PKC isozyme other than PKC alpha, most likely PKC epsilon, is involved in MAPK activation [20].
  • These data show that the Ser252Trp FGFR-2 mutation in Ap syndrome induces constitutive overexpression of PKC-alpha, IL-1alpha, and small GTPase RhoA, suggesting a role for these effectors in osteoblast alterations induced by the mutation [22].

Associations of PRKCA with chemical compounds

  • O(2)(-) release, protein kinase C (PKC) activity, and translocation of PKC-alpha and -betaII and p47phox were increased in THP-1 cells (human monocytic cell line) under HG (15 mmol/l glucose) conditions, whereas AT supplementation inhibited these changes [23].
  • Bradykinin-induced translocation and activation of PKC alpha, but not translocation of PKC epsilon, was blocked in SF 3271 cells which had been incubated with 1-O-hexadecylglycerol (1-O-HDG; 20 micrograms/ml) for 24 h and then incubated in the absence of 1-O-HDG and serum for a further 24 h [20].
  • Moreover, we demonstrate that PKC alpha is constitutively associated with beta(1) integrin [2].
  • The activation of protein kinase C (PKC) increased both MMP-9 activity and expression, which were blocked by some PKC inhibitors (G??6976, bisindolylmaleimide, and Rottlerin), PKC-alpha, and PKC-delta small interfering (si)RNAs but not by hispidin (PKC-beta inhibitor) [24].
  • Thrombin and carbachol cause comparable changes in redistribution of both PKC-alpha and PKC-epsilon [25].

Physical interactions of PRKCA

  • DGK zeta also coimmunoprecipitated with PKC alpha, suggesting that they reside in a regulated signaling complex [26].
  • Treatment of cells with either 10 nM apoE3 or apoE4, 10 microM Abeta (1-42), or apoE/Abeta complexes induced significant translocation of PKC-alpha in both cell types [27].
  • For the first time this result provided the direct evidence that PKC alpha translocated to the cell membrane of thymocytes works as an active second messenger of the T cell receptor-CD3 complex-delivered signal for proliferation and IL-2 production [28].
  • The possibility of PKC-beta(II) being an apoptotic lamin kinase in these cells was further suggested by lamin B1-bound PKC-delta being inactive or only slightly active and by PKC-alpha not combining with the lamin [29].
  • Models of the two zinc-binding modules of PKC alpha are based on nuclear magnetic resonance and crystal structures of such modules in other PKC isoforms while the calcium phospholipid binding module (C2) is based on the crystal structure of a repeating unit in synaptotagmin I [30].

Enzymatic interactions of PRKCA


Regulatory relationships of PRKCA

  • Furthermore, activation of PKC alpha by phorbol 12-myristate 13-acetate inhibited the activity of wild-type DGK zeta, but not DGK zeta S/D, in human embryonic kidney 293 cells [26].
  • Both antisense oligos to PKC-beta and -alpha as well as small interfering RNA (siRNA) to PKC-alpha and -beta resulted in significantly decreased high-glucose-induced IL-6 release [34].
  • Therefore, PKC-alpha-induced PLD activation is unlikely to mediate the effect of NaF [35].
  • The results also indicate that the NaF-induced Arf/RhoA translocation exerts in concert with PMA-activated PKC alpha a synergistic effect on the activation of PLD in Saos-2 cells [35].
  • CONCLUSIONS: VEGF induces disruption of tight junctions in a PKC-alpha dependent manner [36].

Other interactions of PRKCA


Analytical, diagnostic and therapeutic context of PRKCA

  • Immunocytochemistry of brain sections supported these findings and revealed increased neuronal labelling for PKC alpha, PKC gamma and PKC lambda isoforms in neocortex of 16-month-old APPsw mice compared with nontransgenic littermates, with the increase being strongest for PKC gamma and PKC lambda isoforms [39].
  • Immunoblotting with isozyme-specific antibodies indicated the presence of PKC alpha (cytosol only) [40].
  • RESULTS: Immunoprecipitation/kinase (IPK) analysis showed that IL-1alpha increased PKC alpha, delta, and zeta activity 4.5-, 3.1-, and 2.6-fold, respectively, within 5 minutes [41].
  • Protein kinase C-alpha (PKC-alpha) is the kinase responsible for phosphorylating at least two of these serines, based on in vitro kinase assays, peptide mapping, and mutational analysis [42].
  • This increase in expression of PKC alpha was regulated at the message level as demonstrated by Northern blot analysis [43].


  1. 1,25-Dihydroxyvitamin D(3) stimulates activator protein-1-dependent Caco-2 cell differentiation. Chen, A., Davis, B.H., Bissonnette, M., Scaglione-Sewell, B., Brasitus, T.A. J. Biol. Chem. (1999) [Pubmed]
  2. Vascular endothelial growth factor-induced migration of multiple myeloma cells is associated with beta 1 integrin- and phosphatidylinositol 3-kinase-dependent PKC alpha activation. Podar, K., Tai, Y.T., Lin, B.K., Narsimhan, R.P., Sattler, M., Kijima, T., Salgia, R., Gupta, D., Chauhan, D., Anderson, K.C. J. Biol. Chem. (2002) [Pubmed]
  3. Angiotensin II activates extracellular signal regulated kinases via protein kinase C and epidermal growth factor receptor in breast cancer cells. Greco, S., Muscella, A., Elia, M.G., Salvatore, P., Storelli, C., Mazzotta, A., Manca, C., Marsigliante, S. J. Cell. Physiol. (2003) [Pubmed]
  4. Ceramide regulates cellular homeostasis via diverse stress signaling pathways. Ruvolo, P.P. Leukemia (2001) [Pubmed]
  5. Resveratrol antagonizes EGFR-dependent Erk1/2 activation in human androgen-independent prostate cancer cells with associated isozyme-selective PKC alpha inhibition. Stewart, J.R., O'Brian, C.A. Investigational new drugs. (2004) [Pubmed]
  6. Characterization and differential distribution of the three major human protein kinase C isozymes (PKC alpha, PKC beta, and PKC gamma) of the central nervous system in normal and Alzheimer's disease brains. Clark, E.A., Leach, K.L., Trojanowski, J.Q., Lee, V.M. Lab. Invest. (1991) [Pubmed]
  7. Differential regulation of mRNAs encoding protein kinase C isoenzymes in activated human B cells. Brick-Ghannam, C., Ericson, M.L., Schelle, I., Charron, D. Hum. Immunol. (1994) [Pubmed]
  8. Concurrent measures of protein kinase C and phosphoinositides in lithium-treated bipolar patients and healthy individuals: a preliminary study. Soares, J.C., Chen, G., Dippold, C.S., Wells, K.F., Frank, E., Kupfer, D.J., Manji, H.K., Mallinger, A.G. Psychiatry research. (2000) [Pubmed]
  9. Protein kinase C alpha activates RAF-1 by direct phosphorylation. Kolch, W., Heidecker, G., Kochs, G., Hummel, R., Vahidi, H., Mischak, H., Finkenzeller, G., Marmé, D., Rapp, U.R. Nature (1993) [Pubmed]
  10. A role for MARCKS, the alpha isozyme of protein kinase C and myosin I in zymosan phagocytosis by macrophages. Allen, L.H., Aderem, A. J. Exp. Med. (1995) [Pubmed]
  11. Tauroursodeoxycholate inhibits human cholangiocarcinoma growth via Ca2+-, PKC-, and MAPK-dependent pathways. Alpini, G., Kanno, N., Phinizy, J.L., Glaser, S., Francis, H., Taffetani, S., LeSage, G. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  12. Protein kinase C alpha, delta, epsilon and zeta in C6 glioma cells. TPA induces translocation and down-regulation of conventional and new PKC isoforms but not atypical PKC zeta. Chen, C.C. FEBS Lett. (1993) [Pubmed]
  13. Resveratrol regulates cellular PKC alpha and delta to inhibit growth and induce apoptosis in gastric cancer cells. Atten, M.J., Godoy-Romero, E., Attar, B.M., Milson, T., Zopel, M., Holian, O. Investigational new drugs. (2005) [Pubmed]
  14. Protein kinase C isoforms and growth, differentiation and phosphatidylcholine turnover in human neuroblastoma cells. Cook, H.W., Morash, S.C., Rosé, S.D., Ridgway, N.D., Byers, D.M. Journal of lipid mediators and cell signalling. (1996) [Pubmed]
  15. 12(S)-HETE enhancement of prostate tumor cell invasion: selective role of PKC alpha. Liu, B., Maher, R.J., Hannun, Y.A., Porter, A.T., Honn, K.V. J. Natl. Cancer Inst. (1994) [Pubmed]
  16. Refinement of localization of the human genes for myeloperoxidase (MPO), protein kinase C, alpha polypeptide, PRKCA, and the DNA fragment D17S21 on chromosome 17q. Latos-Bielenska, A., Klett, C., Just, W., Hameister, H. Hereditas (1991) [Pubmed]
  17. Novel roles of specific isoforms of protein kinase C in activation of the c-fos serum response element. Soh, J.W., Lee, E.H., Prywes, R., Weinstein, I.B. Mol. Cell. Biol. (1999) [Pubmed]
  18. A protein kinase C cDNA without the regulatory domain is active after transfection in vivo in the absence of phorbol ester. Muramatsu, M., Kaibuchi, K., Arai, K. Mol. Cell. Biol. (1989) [Pubmed]
  19. Distinct nongenomic signal transduction pathways controlled by 17beta-estradiol regulate DNA synthesis and cyclin D(1) gene transcription in HepG2 cells. Marino, M., Acconcia, F., Bresciani, F., Weisz, A., Trentalance, A. Mol. Biol. Cell (2002) [Pubmed]
  20. Evidence that the bradykinin-induced activation of phospholipase D and of the mitogen-activated protein kinase cascade involve different protein kinase C isoforms. Clark, K.J., Murray, A.W. J. Biol. Chem. (1995) [Pubmed]
  21. Heterogeneity of protein kinase C isoenzyme gene expression in human T cell lines. Protein kinase C-beta is not required for several T cell functions. Koretzky, G.A., Wahi, M., Newton, M.E., Weiss, A. J. Immunol. (1989) [Pubmed]
  22. Increased expression of protein kinase Calpha, interleukin-1alpha, and RhoA guanosine 5'-triphosphatase in osteoblasts expressing the Ser252Trp fibroblast growth factor 2 receptor Apert mutation: identification by analysis of complementary DNA microarray. Lomri, A., Lemonnier, J., Delannoy, P., Marie, P.J. J. Bone Miner. Res. (2001) [Pubmed]
  23. Alpha-tocopherol decreases superoxide anion release in human monocytes under hyperglycemic conditions via inhibition of protein kinase C-alpha. Venugopal, S.K., Devaraj, S., Yang, T., Jialal, I. Diabetes (2002) [Pubmed]
  24. Matrix metalloproteinase-9 is differentially expressed in nonfunctioning invasive and noninvasive pituitary adenomas and increases invasion in human pituitary adenoma cell line. Hussaini, I.M., Trotter, C., Zhao, Y., Abdel-Fattah, R., Amos, S., Xiao, A., Agi, C.U., Redpath, G.T., Fang, Z., Leung, G.K., Lopes, M.B., Laws, E.R. Am. J. Pathol. (2007) [Pubmed]
  25. Rapid heterologous desensitization of muscarinic and thrombin receptor-mediated phospholipase D activation. Nieto, M., Kennedy, E., Goldstein, D., Brown, J.H. Mol. Pharmacol. (1994) [Pubmed]
  26. Protein kinase C alpha phosphorylates and negatively regulates diacylglycerol kinase zeta. Luo, B., Prescott, S.M., Topham, M.K. J. Biol. Chem. (2003) [Pubmed]
  27. Effects of apolipoprotein E (apoE) isoforms, beta-amyloid (Abeta) and apoE/Abeta complexes on protein kinase C-alpha (PKC-alpha) translocation and amyloid precursor protein (APP) processing in human SH-SY5Y neuroblastoma cells and fibroblasts. Cedazo-Mínguez, A., Wiehager, B., Winblad, B., Hüttinger, M., Cowburn, R.F. Neurochem. Int. (2001) [Pubmed]
  28. Accelerated proliferation and interleukin-2 production of thymocytes by stimulation of soluble anti-CD3 monoclonal antibody in transgenic mice carrying a rabbit protein kinase C alpha. Iwamoto, T., Hagiwara, M., Hidaka, H., Isomura, T., Kioussis, D., Nakashima, I. J. Biol. Chem. (1992) [Pubmed]
  29. Protein kinase C-beta II Is an apoptotic lamin kinase in polyomavirus-transformed, etoposide-treated pyF111 rat fibroblasts. Chiarini, A., Whitfield, J.F., Armato, U., Dal Pra, I. J. Biol. Chem. (2002) [Pubmed]
  30. Structural aspects of the functional modules in human protein kinase-C alpha deduced from comparative analyses. Srinivasan, N., Bax, B., Blundell, T.L., Parker, P.J. Proteins (1996) [Pubmed]
  31. Phosphorylation of neurofibromin by PKC is a possible molecular switch in EGF receptor signaling in neural cells. Mangoura, D., Sun, Y., Li, C., Singh, D., Gutmann, D.H., Flores, A., Ahmed, M., Vallianatos, G. Oncogene (2006) [Pubmed]
  32. RLIP76 (RALBP1)-mediated transport of leukotriene C4 (LTC4) in cancer cells: implications in drug resistance. Sharma, R., Singhal, S.S., Wickramarachchi, D., Awasthi, Y.C., Awasthi, S. Int. J. Cancer (2004) [Pubmed]
  33. Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C. Ritter, M., Buechler, C., Kapinsky, M., Schmitz, G. Eur. J. Immunol. (2001) [Pubmed]
  34. Hyperglycemia induces monocytic release of interleukin-6 via induction of protein kinase c-{alpha} and -{beta}. Devaraj, S., Venugopal, S.K., Singh, U., Jialal, I. Diabetes (2005) [Pubmed]
  35. Role of protein kinase C alpha, Arf, and cytoplasmic calcium transients in phospholipase D activation by sodium fluoride in osteoblast-like cells. Bourgoin, S.G., Harbour, D., Poubelle, P.E. J. Bone Miner. Res. (1996) [Pubmed]
  36. Disruption of hepatocellular tight junctions by vascular endothelial growth factor (VEGF): a novel mechanism for tumor invasion. Schmitt, M., Horbach, A., Kubitz, R., Frilling, A., Häussinger, D. J. Hepatol. (2004) [Pubmed]
  37. Calcineurin preferentially synergizes with PKC-theta to activate JNK and IL-2 promoter in T lymphocytes. Werlen, G., Jacinto, E., Xia, Y., Karin, M. EMBO J. (1998) [Pubmed]
  38. Structural analysis of human phospholipase D1. Sung, T.C., Zhang, Y., Morris, A.J., Frohman, M.A. J. Biol. Chem. (1999) [Pubmed]
  39. Increased neuronal and glial expression of protein kinase C isoforms in neocortex of transgenic Tg2576 mice with amyloid pathology. Rossner, S., Mehlhorn, G., Schliebs, R., Bigl, V. Eur. J. Neurosci. (2001) [Pubmed]
  40. Expression, subcellular distribution and response to phorbol esters of protein kinase C (PKC) isozymes in drug-sensitive and multidrug-resistant KB cells evidence for altered regulation of PKC-alpha. Cloud-Heflin, B.A., McMasters, R.A., Osborn, M.T., Chambers, T.C. Eur. J. Biochem. (1996) [Pubmed]
  41. IL-1alpha-induced COX-2 expression in human intestinal myofibroblasts is dependent on a PKCzeta-ROS pathway. Di Mari, J.F., Mifflin, R.C., Adegboyega, P.A., Saada, J.I., Powell, D.W. Gastroenterology (2003) [Pubmed]
  42. Protein kinase C-alpha phosphorylation of specific serines in the connecting segment of the beta 4 integrin regulates the dynamics of type II hemidesmosomes. Rabinovitz, I., Tsomo, L., Mercurio, A.M. Mol. Cell. Biol. (2004) [Pubmed]
  43. Selective regulation of expression of protein kinase C (PKC) isoenzymes in multidrug-resistant MCF-7 cells. Functional significance of enhanced expression of PKC alpha. Blobe, G.C., Sachs, C.W., Khan, W.A., Fabbro, D., Stabel, S., Wetsel, W.C., Obeid, L.M., Fine, R.L., Hannun, Y.A. J. Biol. Chem. (1993) [Pubmed]
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