PKCtheta: A potential therapeutic target for T-cell-mediated diseases.
Protein kinase (PK)Ctheta belongs to the calcium-independent novel subfamily of PKCs, which itself is a member of the cAMP-dependent, cGMP-dependent PKC kinase superfamily. As a critical regulator of T-cell receptor (TCR) signaling, PKCtheta is required for mature T-cell activation. PKCtheta regulates helper T-cell (Th)2-dependent pulmonary inflammation and airway hyperresponsiveness following immunization and lung challenge with ovalbumin in vivo, and controls Th1 cells in experimental autoimmune encephalomyelitis. Its selective role in T-cell effector function and the TCR signalosome, although not in T-cell development, makes PKCtheta an attractive therapeutic target in T-cell-mediated disease processes. This review discusses the regulation and role of PKCtheta in T-cell-mediated diseases.
Chaudhary
Divya
D
Wyeth Research, 87 Cambridge Park Drive, Cambridge, MA 02140 USA. dchaudhary@wyeth.com
Kasaian
Marion
M
D000818:Animals; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*
D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D011948:Receptors, Antigen, T-Cell; C076233:PRKCQ protein, human; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta