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Gene Review

Prkcq  -  protein kinase C, theta

Mus musculus

Synonyms: A130035A12Rik, AW494342, PKC theta, PKC-0, PKC-theta, ...

PKC-theta is a member of the Protein Kinase C family of serine/threonine kinase activated by elevated levels of di-acyl-glycerol (DAG) and Calcium. In mammals, PKC-theta is only expressed in cells of the immune system and in skeletal muscles. When PKC-theta is activated in cells of the immune system, such as T and B cells, it mediates NF-Kappa B signaling in parallel to the kinase Akt.

PKC-theta Activation in T and B Cells. The elevated levels of DAG and calcium needed for PKC-theta activation are generated by the PI3K pathway. PI3K, phosphorylates phospho-inositol lipids in the membrane to generate DAG and PIP3, which activates Akt and opens Calcium channels in the membrane of the Endoplasmic/Sarcoplasmic Reticulum (ER or SR), as a result Calcium enters the cytoplasm.

PI3K is activated by active T-cell Receptor (TCR) or B-Cell Receptor (BCR) signaling, these receptors are multi-complexes on the cellular membrane of T and B cells that bind antigen with incredible specificity that is achieved by a process of DNA recombination during T and B cell development in the Thymus or bone marrow, respectively. This process of recombination and differentiation is astonishingly complex and a remarkable feat of evolution. These cells have evolved to protect us from any foreign-antigen carrying pathogen, even thous that we have never met or are yet to have evolved.

The Role of PKC-theta in Immunological Synapse Stability and Motility. The Immunological Synapse (IS) is structure of multi-protein complexes that forms on the membrane interface between two interacting cells of the immune system. The IS that forms between Antigen Presenting Cells (APC) and T cells is a key stage in the activation of almost any type of an immune response. This interaction takes place in the lymph nodes after an APC presenting a foreign pathogen peptide (a peptide is a short sequence of amino acids or a small protein molecule) is specifically recognized by a specific TCR carrying T cell, resulting in signaling events in both cells. This signaling process is a fundamental stage in the immune response, because the T cell needs to gather information about the type of pathogen the APC encountered, activate it self, make a molecular decision about what kind of immune response is needed, pass this information back to the APC and then proliferate and distribute the information so an immune response can be generated. All of the above communicative events happen in the IS, the interaction is both through direct binding and ligand-receptor binding. The ligands secreted by active T-cells and other immune cells are known as cytokines that very according to the type of cell and the type of immune response generated.

So, what does PKC-theta have to do with the IS, apart from activating T and B cells through NF-Kappa B signaling? It turns-out that the localization of PKC-theta in the IS determines whether the T-cells are going to be motile and form short-lived IS interactions or stable. In T-cells, if PKC-theta localization is surrounding the center of the IS, the cells or more motile and form less stable synapses. But, if PKC-theta is excluded from the IS, the T-cells form very stable IS. This is crucial because activated T-cells secret cytokines and if the IS is stable the T-cell will secret in a more directed manner as apposed to a more dispersed secretion. Effector T-cell that form unstable IS, known as Kinapses, secret in a dispersed manner and are more inflammatory then less motile cells. Contradictory to Effector T-cells, Regulatory T-cells (cells that regulate and inactivate effector T-cells) are more effective and better inhibit inflammation, when stable IS are formed.

By inhibiting PKC-theta, it is possible to inhibit Effector T-cell inflammatory effect both directly, through inhibiting NF-Kappa B activation and reduced motility, and indirectly, by improved Regulatory T-cell function. This is a promising unti-inflammatory drug development opportunity, that might help the treatment of Auto-immune diseases or graft vs host disease in the future

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Disease relevance of Prkcq


High impact information on Prkcq



Biological context of Prkcq


Anatomical context of Prkcq


Associations of Prkcq with chemical compounds


Physical interactions of Prkcq


Regulatory relationships of Prkcq


Other interactions of Prkcq


Analytical, diagnostic and therapeutic context of Prkcq




  1. Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse. Sims, T.N., Soos, T.J., Xenias, H.S., Dubin-Thaler, B., Hofman, J.M., Waite, J.C., Cameron, T.O., Thomas, V.K., Varma, R., Wiggins, C.H., Sheetz, M.P., Littman, D.R., Dustin, M.L. Cell. (2007) [Pubmed]
  2. Protein kinase C-theta mediates negative feedback on regulatory T cell function. Zanin-Zhorov, A., Ding, Y., Kumari, S., Attur, M., Hippen, K.L., Brown, M., Blazar, B.R., Abramson, S.B., Lafaille, J.J., Dustin, M.L. Science. (2010) [Pubmed]
  3. PKC theta mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia. Felli, M.P., Vacca, A., Calce, A., Bellavia, D., Campese, A.F., Grillo, R., Di Giovine, M., Checquolo, S., Talora, C., Palermo, R., Di Mario, G., Frati, L., Gulino, A., Screpanti, I. Oncogene (2005) [Pubmed]
  4. Transgenic mice with dominant negative PKC-theta in skeletal muscle: a new model of insulin resistance and obesity. Serra, C., Federici, M., Buongiorno, A., Senni, M.I., Morelli, S., Segratella, E., Pascuccio, M., Tiveron, C., Mattei, E., Tatangelo, L., Lauro, R., Molinaro, M., Giaccari, A., Bouché, M. J. Cell. Physiol. (2003) [Pubmed]
  5. Mice deficient in PKC theta demonstrate impaired in vivo T cell activation and protection from T cell-mediated inflammatory diseases. Anderson, K., Fitzgerald, M., Dupont, M., Wang, T., Paz, N., Dorsch, M., Healy, A., Xu, Y., Ocain, T., Schopf, L., Jaffee, B., Picarella, D. Autoimmunity (2006) [Pubmed]
  6. Protein kinase C-theta isoenzyme selective stimulation of the transcription factor complex AP-1 in T lymphocytes. Baier-Bitterlich, G., Uberall, F., Bauer, B., Fresser, F., Wachter, H., Grunicke, H., Utermann, G., Altman, A., Baier, G. Mol. Cell. Biol. (1996) [Pubmed]
  7. NOTCH1 promotes T cell leukemia-initiating activity by RUNX-mediated regulation of PKC-θ and reactive oxygen species. Giambra, V., Jenkins, C.R., Wang, H., Lam, S.H., Shevchuk, O.O., Nemirovsky, O., Wai, C., Gusscott, S., Chiang, M.Y., Aster, J.C., Humphries, R.K., Eaves, C., Weng, A.P. Nat. Med. (2012) [Pubmed]
  8. PKC-theta is required for TCR-induced NF-kappaB activation in mature but not immature T lymphocytes. Sun, Z., Arendt, C.W., Ellmeier, W., Schaeffer, E.M., Sunshine, M.J., Gandhi, L., Annes, J., Petrzilka, D., Kupfer, A., Schwartzberg, P.L., Littman, D.R. Nature (2000) [Pubmed]
  9. DOCK2 is essential for antigen-induced translocation of TCR and lipid rafts, but not PKC-theta and LFA-1, in T cells. Sanui, T., Inayoshi, A., Noda, M., Iwata, E., Oike, M., Sasazuki, T., Fukui, Y. Immunity (2003) [Pubmed]
  10. Akt provides the CD28 costimulatory signal for up-regulation of IL-2 and IFN-gamma but not TH2 cytokines. Kane, L.P., Andres, P.G., Howland, K.C., Abbas, A.K., Weiss, A. Nat. Immunol. (2001) [Pubmed]
  11. PKC-theta knockout mice are protected from fat-induced insulin resistance. Kim, J.K., Fillmore, J.J., Sunshine, M.J., Albrecht, B., Higashimori, T., Kim, D.W., Liu, Z.X., Soos, T.J., Cline, G.W., O'Brien, W.R., Littman, D.R., Shulman, G.I. J. Clin. Invest. (2004) [Pubmed]
  12. Conventional PKC-alpha, novel PKC-epsilon and PKC-theta, but not atypical PKC-lambda are MARCKS kinases in intact NIH 3T3 fibroblasts. Uberall, F., Giselbrecht, S., Hellbert, K., Fresser, F., Bauer, B., Gschwendt, M., Grunicke, H.H., Baier, G. J. Biol. Chem. (1997) [Pubmed]
  13. CD28 plays a critical role in the segregation of PKC theta within the immunologic synapse. Huang, J., Lo, P.F., Zal, T., Gascoigne, N.R., Smith, B.A., Levin, S.D., Grey, H.M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  14. PKC-theta-deficient mice are protected from Th1-dependent antigen-induced arthritis. Healy, A.M., Izmailova, E., Fitzgerald, M., Walker, R., Hattersley, M., Silva, M., Siebert, E., Terkelsen, J., Picarella, D., Pickard, M.D., LeClair, B., Chandra, S., Jaffee, B. J. Immunol. (2006) [Pubmed]
  15. Protein kinase C-theta-mediated signals enhance CD4+ T cell survival by up-regulating Bcl-xL. Manicassamy, S., Gupta, S., Huang, Z., Sun, Z. J. Immunol. (2006) [Pubmed]
  16. A new member of the protein kinase C family, nPKC theta, predominantly expressed in skeletal muscle. Osada, S., Mizuno, K., Saido, T.C., Suzuki, K., Kuroki, T., Ohno, S. Mol. Cell. Biol. (1992) [Pubmed]
  17. Resistance to experimental autoimmune encephalomyelitis and impaired IL-17 production in protein kinase C theta-deficient mice. Tan, S.L., Zhao, J., Bi, C., Chen, X.C., Hepburn, D.L., Wang, J., Sedgwick, J.D., Chintalacharuvu, S.R., Na, S. J. Immunol. (2006) [Pubmed]
  18. Vav regulates peptide-specific apoptosis in thymocytes. Kong, Y.Y., Fischer, K.D., Bachmann, M.F., Mariathasan, S., Kozieradzki, I., Nghiem, M.P., Bouchard, D., Bernstein, A., Ohashi, P.S., Penninger, J.M. J. Exp. Med. (1998) [Pubmed]
  19. Overexpression of nPKC theta is inhibitory for agrin-induced nicotinic acetylcholine receptor clustering in C2C12 myotubes. Miles, K., Wagner, M. J. Neurosci. Res. (2003) [Pubmed]
  20. SAP regulates T(H)2 differentiation and PKC-theta-mediated activation of NF-kappaB1. Cannons, J.L., Yu, L.J., Hill, B., Mijares, L.A., Dombroski, D., Nichols, K.E., Antonellis, A., Koretzky, G.A., Gardner, K., Schwartzberg, P.L. Immunity (2004) [Pubmed]
  21. The Critical Role of Protein Kinase C-{theta} in Fas/Fas Ligand-Mediated Apoptosis. Manicassamy, S., Sun, Z. J. Immunol. (2007) [Pubmed]
  22. Requirement for CARMA1 in antigen receptor-induced NF-kappa B activation and lymphocyte proliferation. Egawa, T., Albrecht, B., Favier, B., Sunshine, M.J., Mirchandani, K., O'Brien, W., Thome, M., Littman, D.R. Curr. Biol. (2003) [Pubmed]
  23. Protein kinase C theta is critical for the development of in vivo T helper (Th)2 cell but not Th1 cell responses. Marsland, B.J., Soos, T.J., Späth, G., Littman, D.R., Kopf, M. J. Exp. Med. (2004) [Pubmed]
  24. Effect of fever-like whole-body hyperthermia on lymphocyte spectrin distribution, protein kinase C activity, and uropod formation. Wang, X.Y., Ostberg, J.R., Repasky, E.A. J. Immunol. (1999) [Pubmed]
  25. Developmental regulation of a protein kinase C isoform localized in the neuromuscular junction. Hilgenberg, L., Miles, K. J. Cell. Sci. (1995) [Pubmed]
  26. Unique expression pattern of protein kinase C-theta: high mRNA levels in normal mouse testes and in T-lymphocytic cells and neoplasms. Mischak, H., Goodnight, J., Henderson, D.W., Osada, S., Ohno, S., Mushinski, J.F. FEBS Lett. (1993) [Pubmed]
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