Protein kinase C-theta (PKC theta): a key enzyme in T cell life and death.
The novel protein kinase C (PKC) isoform, PKC theta, is expressed in a relatively selective manner in T lymphocytes (and muscle). Recent analysis of this PKC isotype in T cells and the characterization of PKC theta-deficient mice revealed important clues about its function and regulation. PKC theta does not have an obvious role in T cell development, but it is essential for the activation of mature T cells. The requirement of PKC theta for T cell activation, proliferation and cytokine production reflects the essential role of this isotype in inducing signaling pathways leading to the activation of the transcription factors AP-1 and NF-kappa B in a T cell-specific manner. A unique feature of PKC theta is its highly selective translocation to the central region of the immunological synapse (IS) in antigen-stimulated T cells, a property apparently important for its proper signaling functions. This localization implies unique pathway(s) that regulate the translocation and/or activation of this enzyme. Our work suggests that sustained PKC theta membrane translocation and phosphorylation are relatively independent of phospholipase C (PLC) activation and diacylglycerol (DAG) production. Instead, a pathway that requires Vav, phosphatidylinositol 3-kinase (PI3-K), Rac1 and actin cytoskeleton reorganization mediates these events. Additionally, PKC theta provides an important survival signal to T cells. Nevertheless, several questions regarding the function and regulation of PKC theta and the identity of its immediate targets/substrates remain open. Resolution of these questions could open the way to the development of selective PKC theta inhibitors, which may have therapeutic potential in immunological diseases and in cancer.
Altman
Amnon
A
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, Science Center Dr., San Diego, CA 92121, USA. amnon@liai.org
Villalba
Martin
M
D000818:Animals; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D018106:CD28 Antigens; D007376:Interleukin-2; D007527:Isoenzymes; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases