PKC ACTIVITY AND PROTEIN-PHOSPHORYLATION IN REGULATION OF SIG MEDIATED B-CELL ACTIVATION

The inhibitory and stimulatory elements of cellular signalling associa ted with activation of protein kinase C (PKC) in murine B lymphocytes were investigated by employing two PKC activators with opposing effect s on cell proliferation. Being an inhibitor of anti-Ig mediated prolif eration, the phorbol ester PDBU induced a more substantial translocati on of cytosolic PKC activity than the alkaloid PKC activator indolacta m, which enhances anti-Ig mediated B cell proliferation. PDBU and indo lactam were equally effective kinase activators, as determined by P-32 incorporation of the substrate proteins. Concentrations of indolactam which induced an inhibition of anti-Ig mediated B cell proliferation also induced a precipitous decline in detergent soluble cellular PKC a ctivity, which was comparable with 1 mu M PDBU. The induced phosphopro tein patterns were similar, with an exception of the nuclear envelope protein lamin B, which was prominently phosphorylated by PDBU but not by stimulatory concentrations of indolactam. The enhanced phosphorylat ion of lamin B was associated with cellular growth arrest: inhibitory concentrations of indolactam induced the phosphorylation of lamin B eq ual to PDBU, whereas an increased phosphorylation of lamin B was never observed upon stimulation with anti-Ig. Together, inhibition of anti- Ig mediated B cell proliferation was related to down-regulation of cyt oplasmic PKC and induction of nuclear PKC-dependent phosphorylation.