PROTEIN-KINASE-C ISOTYPE-THETA, ISOTYPE-DELTA AND ISOTYPE-ETA IN HUMAN-LYMPHOCYTES - DIFFERENTIAL RESPONSES TO SIGNALING THROUGH THE T-CELLRECEPTOR AND PHORBOL ESTERS

The repertoire of novel and atypical protein kinase C (PKC) isotypes p resent in human T cells and their subcellular localization have not be en fully characterized. We detected calcium-independent PKC activity i n whole cell fractions from unstimulated peripheral blood lymphocytes (PBL). Towards an understanding of the role of PKC isoforms in lymphoc yte activation we have studied the expression of calcium-independent P KC isoforms theta, delta and eta in PBL. With isoform-specific antibod ies we detected the presence of PKC theta and delta in whole cell frac tions from unstimulated human PBL by Western blot analysis. In additio n, immunocytochemical analysis confirmed the presence of the novel PKC isoform PKC eta in PBL. Using immunocytochemistry, PKC theta, delta a nd eta had distinct patterns of redistribution following activation by phorbol myristate acetate (PMA). However, signalling through the T-ce ll receptor (TCR) did not appear to induce such changes in isoenzyme r edistribution. These findings indicate that activation of lymphocytes either through the TCR-CD3 complex or with PMA induces different signa lling pathways with respect to calcium-independent isoenzymes. Signall ing through receptors other than the CD3 complex may be involved in ac tivation of these isotypes.