NEW PERSPECTIVES ON PKC-THETA, A MEMBER OF THE NOVEL SUBFAMILY OF PROTEIN-KINASE-C

Members of the protein kinase C (PKC) family of serine/threonine prote in kinases have been implicated in numerous cellular responses in a la rge variety of cell types, Expression patterns of individual members a nd differences in their cofactor requirements and potential substrate specificity suggest that each isoenzyme may be involved in specific re gulatory processes. The PKC theta isoenzyme exhibits a relatively rest ricted expression pattern with high protein levels found predominantly in hematopoietic cells and skeletal muscle. PKC theta was found to be expressed in T, but not B lymphocytes, and to colocalize with the T-c ell antigen receptor (TCR) at the site of contact between the antigen- responding T cell and the antigen-presenting cell (APC). Colocalizatio n of PKC theta with the TCR was selective for this isoenzyme and occur red only upon antigen-mediated responses leading to T-cell activation and proliferation. PKC theta was found to be involved in the regulatio n of transcriptional activation of early-activation genes, predominant ly AP-I, and its cellular distribution and activation were found to be regulated by the 14-3-3 protein. Other findings indicated that PKC th eta can associate with the HIV negative factor (Nef) protein, suggesti ng that altered regulation of PKC theta by Nef may contribute to the T cell impairments that are characteristic of infection by HIV. PKC the ta is expressed at relatively high levels in skeletal muscle, where it is suggested to play a role in signal transduction in both the develo ping and mature neuromuscular junction. In addition, PKC theta appears to be involved in the insulin-mediated response of intact skeletal mu scle, as well as in experimentally induced insulin resistance of skele tal muscle. Further studies suggest that PKC theta is expressed in end othelial cells and is involved in multiple processes essential for ang iogenesis and wound healing, including the regulation of cell cycle pr ogression, formation and maintenance of actin cytoskeleton, and format ion of capillary tubes. Here, me review recent progress in the study o f PKC theta and discuss its potential role in various cellular respons es.