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Gene Review

PRKCB  -  protein kinase C, beta

Homo sapiens

Synonyms: PKC-B, PKC-beta, PKCB, PRKCB1, PRKCB2, ...
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Disease relevance of PRKCB1


High impact information on PRKCB1

  • B cell antigen receptor (BCR) engagement led to the progressive recruitment of CARMA1 into lipid rafts and to the association of CARMA1 with, and phosphorylation by, PKCbeta [5].
  • Furthermore, PKCbeta interacted with the serine-rich CARMA1 linker, and both PKCbeta and PKCtheta phosphorylated identical serine residues (S564, S649, and S657) within this linker [5].
  • In normal T cells and T lymphoma cell lines, this type of motility is accompanied by PKC-beta-sensitive cytoskeletal rearrangements and the formation of trailing cell extensions, which are supported by microtubules [6].
  • Expression of PKC-beta(I) and enhanced green fluorescent protein (EGFP) in nonmotile PKC-beta-deficient T cells restored their locomotory behavior in response to a triggering stimulus delivered via LFA-1 and correlated directly with the degree of cell polarization [6].
  • E2-CD81 interaction stimulates translocation of PKC-beta to lipid rafts, thereby preventing its association with the centrosome and microtubule cytoskeleton, which is crucial to the process of T-cell migration [7].

Chemical compound and disease context of PRKCB1


Biological context of PRKCB1


Anatomical context of PRKCB1

  • By Western blot analysis, the racially determined pigment level in cultured melanocytes correlated with PKC-beta protein expression [2].
  • These data contribute to our developing understanding of the signal transduction pathways involved in the chemotactic response of human monocytes to MCP-1 and uniquely identify the requirement for the PKCbeta isoform in this important process [14].
  • The most significant findings were decreased PKC-beta expression in early neoplasia when compared to benign epithelium (P < 0.0001), together with a reciprocal increase in expression of PKC-epsilon (P < 0.0001) [15].
  • The phosphorylation also occurred on endogenous SHP2 in Chinese hamster ovary (CHO) cells stably overexpressing PKC beta 2 [16].
  • In resting lymphocytes of elderly subjects PKC-zeta and -epsilon were almost equally distributed between the cytosolic and the membrane fractions, whereas PKC-alpha and -zeta were mainly found in the membrane fraction and PKC-beta was almost exclusively located in the cytosolic fraction [17].

Associations of PRKCB1 with chemical compounds

  • 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) [18].
  • When a phosphatidylinositol (4,5) bisphosphate-derived DAG pool was generated in the nucleus, a selective translocation of PKC-beta II occurred [19].
  • Our data define a procarcinogenic PKC beta II --> Cox-2 --> TGF-beta signaling axis within the colonic epithelium, and provide a molecular mechanism by which dietary omega-3 fatty acids and nonsteroidal antiinflammatory agents such as Celecoxib suppress colon carcinogenesis [20].
  • Furthermore, PKC phosphorylation of SHP2 was completely blocked by the PKC inhibitor bisindolylmaleimide and was not detectable when SHP2 was co-overexpressed with kinase negative mutants of PKC beta 1 and -beta 2 [16].
  • Tyrosinase, the key enzyme in melanogenesis, is activated when protein kinase C-beta (PKC-beta) phosphorylates the serine residues at amino acid positions 505 and 509 [21].

Physical interactions of PRKCB1

  • UV/DECA treatment of synthetic peptides modeled after the RACK-1-binding site in the C2 region of PKC beta induced modification of Ser218-Leu-Asn-Pro-Glu-Trp-Asn-Glu-Thr226, but not of a control peptide [22].
  • The data show that the classical PKC isoenzymes, alpha and beta, were activated by TPA and at a time prior to NADPH oxidase complex assembly. fMLP induced activation of PKC-beta over a similar time course [23].

Enzymatic interactions of PRKCB1

  • To investigate the mechanism by which only PKC-beta phosphorylates tyrosinase, we examined the expression of receptor for activated C-kinase-I (RACK-I), a receptor specific for activated PKC-beta, on the surface of melanosomes, the specialized organelle in which melanogenesis occurs [24].
  • The conventional PKC beta 1 and the novel PKCs delta and epsilon effectively phosphorylated recombinant GAP-43 in vitro; atypical PKC zeta did not [25].
  • The results also demonstrated that PKCbeta phosphorylated and activated MEKK-1 in vitro [26].

Regulatory relationships of PRKCB1

  • The ability of Smad6s to regulate the TGF-beta promoter and subsequent PAI-1 induction was suppressed by a selective protein kinase C-beta (PKC-beta) inhibitor [27].
  • However, in contrast with MITF-M, MITF-A failed to transactivate co-expressed PKC-beta/CAT or CAT constructs under the control of a full-length tyrosinase promoter [28].
  • 2. NIDDM patients differ in their PKC beta 2-responses to glucose and 3. poor metabolic control leads to moderate downregulation of PKC alpha suggesting continued activation [29].
  • We conclude that 1. acute elevation of glucose by 5.5 mmol/L or more can activate PKC beta 2 translocation in controls and NIDDM patients in vivo irrespective of parameters of metabolic control [29].
  • These data indicate that VEGF-mediated disruption of endothelial cell-cell interactions requires activation of PKC beta isoforms and that this pathway is blocked by Ang1 [30].

Other interactions of PRKCB1

  • Detectable levels of PKC-alpha and PKC-zeta were also significantly increased in the cancers (P = 0.045 and P = 0.015 respectively) but did not correlate with either PKC-beta or PKC-epsilon for individual cases [15].
  • Transfecting HL-525 cells with a PKC-beta expression plasmid restored PKC-beta levels and PMA inducibility of cell adhesion and spreading as well as MMP-9 gene expression [31].
  • Further studies evaluating the calcium response that is triggered upon MCP-1 interaction with its receptor, CCR2, indicate that this response is not altered by antisense or sense ODN treatment, thus supporting our hypothesis that PKCbeta is critical for post-receptor signal transduction downstream of the immediate calcium signal [14].
  • PKC-beta I and -beta II were expressed exclusively in normal melanocytes but not in melanoma cells, whereas PKC-gamma was not found in any of the cultures studied [32].
  • Assay of PKC beta1 kinase activity indicated that the binding of the PH domain of GRK2 to PKC beta 1 could down-regulate activity of PKC beta 1 kinase [33].

Analytical, diagnostic and therapeutic context of PRKCB1


  1. Identification of a common risk haplotype for diabetic nephropathy at the protein kinase C-beta1 (PRKCB1) gene locus. Araki, S., Ng, D.P., Krolewski, B., Wyrwicz, L., Rogus, J.J., Canani, L., Makita, Y., Haneda, M., Warram, J.H., Krolewski, A.S. J. Am. Soc. Nephrol. (2003) [Pubmed]
  2. The beta isoform of protein kinase C stimulates human melanogenesis by activating tyrosinase in pigment cells. Park, H.Y., Russakovsky, V., Ohno, S., Gilchrest, B.A. J. Biol. Chem. (1993) [Pubmed]
  3. Polymorphisms of the protein kinase C-beta gene (PRKCB1) accelerate kidney disease in type 2 diabetes without overt proteinuria. Araki, S., Haneda, M., Sugimoto, T., Isono, M., Isshiki, K., Kashiwagi, A., Koya, D. Diabetes Care (2006) [Pubmed]
  4. Protein kinase C: a novel target for inhibiting gastric cancer cell invasion. Schwartz, G.K., Jiang, J., Kelsen, D., Albino, A.P. J. Natl. Cancer Inst. (1993) [Pubmed]
  5. Phosphorylation of the CARMA1 linker controls NF-kappaB activation. Sommer, K., Guo, B., Pomerantz, J.L., Bandaranayake, A.D., Moreno-García, M.E., Ovechkina, Y.L., Rawlings, D.J. Immunity (2005) [Pubmed]
  6. Crucial importance of PKC-beta(I) in LFA-1-mediated locomotion of activated T cells. Volkov, Y., Long, A., McGrath, S., Ni Eidhin, D., Kelleher, D. Nat. Immunol. (2001) [Pubmed]
  7. The hepatitis C envelope 2 protein inhibits LFA-1-transduced protein kinase C signaling for T-lymphocyte migration. Volkov, Y., Long, A., Freeley, M., Golden-Mason, L., O'Farrelly, C., Murphy, A., Kelleher, D. Gastroenterology (2006) [Pubmed]
  8. The modulation of growth by HMBA in PKC overproducing HT29 colon cancer cells. Choi, P.M., Weinstein, I.B. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  9. ACTH and phorbol ester stimulated redistribution of protein kinase C in human cortisol-producing adrenal adenoma. Kajita, K., Ishizuka, T., Yamamoto, M., Nagashima, T., Taniguchi, O., Mune, T., Murayama, M., Kitagawa, S., Yasuda, K. Endocr. J. (1994) [Pubmed]
  10. The phorbol ester TPA markedly enhances the binding of calcium to the regulatory domain of protein kinase C beta 1 in the presence of phosphatidylserine. Luo, J.H., Xing, W.Q., Weinstein, I.B. Carcinogenesis (1995) [Pubmed]
  11. PKC-B inhibition: a new therapeutic approach for diabetic complications? Avignon, A., Sultan, A. Diabetes Metab. (2006) [Pubmed]
  12. Haplotypes in the gene encoding protein kinase c-beta (PRKCB1) on chromosome 16 are associated with autism. Philippi, A., Roschmann, E., Tores, F., Lindenbaum, P., Benajou, A., Germain-Leclerc, L., Marcaillou, C., Fontaine, K., Vanpeene, M., Roy, S., Maillard, S., Decaulne, V., Saraiva, J.P., Brooks, P., Rousseau, F., Hager, J. Mol. Psychiatry (2005) [Pubmed]
  13. Protein kinase C betaII plays an essential role in dendritic cell differentiation and autoregulates its own expression. Cejas, P.J., Carlson, L.M., Zhang, J., Padmanabhan, S., Kolonias, D., Lindner, I., Haley, S., Boise, L.H., Lee, K.P. J. Biol. Chem. (2005) [Pubmed]
  14. Protein kinase C beta is required for human monocyte chemotaxis to MCP-1. Carnevale, K.A., Cathcart, M.K. J. Biol. Chem. (2003) [Pubmed]
  15. Protein kinase C isoenzyme patterns characteristically modulated in early prostate cancer. Cornford, P., Evans, J., Dodson, A., Parsons, K., Woolfenden, A., Neoptolemos, J., Foster, C.S. Am. J. Pathol. (1999) [Pubmed]
  16. The Protein-tyrosine-phosphatase SHP2 is phosphorylated on serine residues 576 and 591 by protein kinase C isoforms alpha, beta 1, beta 2, and eta. Strack, V., Krützfeldt, J., Kellerer, M., Ullrich, A., Lammers, R., Häring, H.U. Biochemistry (2002) [Pubmed]
  17. Cellular distribution of protein kinase C isozymes in CD3-mediated stimulation of human T lymphocytes with aging. Fulop, T., Leblanc, C., Lacombe, G., Dupuis, G. FEBS Lett. (1995) [Pubmed]
  18. 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]
  19. Proliferating or differentiating stimuli act on different lipid-dependent signaling pathways in nuclei of human leukemia cells. Neri, L.M., Bortul, R., Borgatti, P., Tabellini, G., Baldini, G., Capitani, S., Martelli, A.M. Mol. Biol. Cell (2002) [Pubmed]
  20. Role of cyclooxygenase 2 in protein kinase C beta II-mediated colon carcinogenesis. Yu, W., Murray, N.R., Weems, C., Chen, L., Guo, H., Ethridge, R., Ceci, J.D., Evers, B.M., Thompson, E.A., Fields, A.P. J. Biol. Chem. (2003) [Pubmed]
  21. Protein kinase C-beta-mediated complex formation between tyrosinase and TRP-1. Wu, H., Park, H.Y. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  22. Photoinduced inactivation of protein kinase C by dequalinium identifies the RACK-1-binding domain as a recognition site. Rotenberg, S.A., Sun, X.G. J. Biol. Chem. (1998) [Pubmed]
  23. Superoxide production in human neutrophils: evidence for signal redundancy and the involvement of more than one PKC isoenzyme class. Pongracz, J., Lord, J.M. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  24. The receptor for activated C-kinase-I (RACK-I) anchors activated PKC-beta on melanosomes. Park, H.Y., Wu, H., Killoran, C.E., Gilchrest, B.A. J. Cell. Sci. (2004) [Pubmed]
  25. Phosphorylation of GAP-43 (growth-associated protein of 43 kDa) by conventional, novel and atypical isotypes of the protein kinase C gene family: differences between oligopeptide and polypeptide phosphorylation. Oehrlein, S.A., Parker, P.J., Herget, T. Biochem. J. (1996) [Pubmed]
  26. Functional role for protein kinase Cbeta as a regulator of stress-activated protein kinase activation and monocytic differentiation of myeloid leukemia cells. Kaneki, M., Kharbanda, S., Pandey, P., Yoshida, K., Takekawa, M., Liou, J.R., Stone, R., Kufe, D. Mol. Cell. Biol. (1999) [Pubmed]
  27. Smad6s regulates plasminogen activator inhibitor-1 through a protein kinase C-beta-dependent up-regulation of transforming growth factor-beta. Berg, D.T., Myers, L.J., Richardson, M.A., Sandusky, G., Grinnell, B.W. J. Biol. Chem. (2005) [Pubmed]
  28. MITF mediates cAMP-induced protein kinase C-beta expression in human melanocytes. Park, H.Y., Wu, C., Yonemoto, L., Murphy-Smith, M., Wu, H., Stachur, C.M., Gilchrest, B.A. Biochem. J. (2006) [Pubmed]
  29. Activation of human platelet protein kinase C-beta 2 in vivo in response to acute hyperglycemia. Pirags, V., Assert, R., Haupt, K., Schatz, H., Pfeiffer, A. Exp. Clin. Endocrinol. Diabetes (1996) [Pubmed]
  30. Opposing effect of angiopoietin-1 on VEGF-mediated disruption of endothelial cell-cell interactions requires activation of PKC beta. Wang, Y., Pampou, S., Fujikawa, K., Varticovski, L. J. Cell. Physiol. (2004) [Pubmed]
  31. Fibronectin-mediated cell adhesion is required for induction of 92-kDa type IV collagenase/gelatinase (MMP-9) gene expression during macrophage differentiation. The signaling role of protein kinase C-beta. Xie, B., Laouar, A., Huberman, E. J. Biol. Chem. (1998) [Pubmed]
  32. Lack of protein kinase C (PKC)-beta and low PKC-alpha, -delta, -epsilon, and -zeta isozyme levels in proliferating human melanoma cells. Krasagakis, K., Fimmel, S., Genten, D., Eberle, J., Quas, P., Ziegler, W., Haller, H., Orfanos, C.E. Int. J. Oncol. (2002) [Pubmed]
  33. PH domain of G protein-coupled receptor kinase-2 binds to protein kinase C (PKC) and negatively regulates activity of PKC kinase. Ji, S., Liu, X., Li, S., Shen, L., Li, F., Wang, J., Han, J., Yao, L. Front. Biosci. (2003) [Pubmed]
  34. Protein kinase C (PKC) activity and PKC messenger RNAs in human pituitary adenomas. Jin, L., Maeda, T., Chandler, W.F., Lloyd, R.V. Am. J. Pathol. (1993) [Pubmed]
  35. Protein kinase C (PKC) activation via human leucocyte antigen class II molecules. A novel regulation of PKC activity. Brick-Ghannam, C., Huang, F.L., Temime, N., Charron, D. J. Biol. Chem. (1991) [Pubmed]
  36. Protein kinase C-beta activates tyrosinase by phosphorylating serine residues in its cytoplasmic domain. Park, H.Y., Perez, J.M., Laursen, R., Hara, M., Gilchrest, B.A. J. Biol. Chem. (1999) [Pubmed]
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