EFFECT OF PROTEIN-KINASE-C INHIBITORS ON TPA-INDUCED INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION AND INDUCTION OF TRANSFORMED MORPHOLOGY IN SYRIAN-HAMSTER EMBRYO CELLS

Staurosporine and H-7, but not polymyxin B, were found partly to suppr ess the effect of TPA on both inhibition of gap junctional intercellul ar communication (GJIC), down-regulation of EGF-binding and induction of transformed morphology in Syrian hamster embryo (SHE) cells. The pa rallel effect of these kinase inhibitors suggests that TPA induces the effects through activation of protein kinase C (PKC). This is consist ent with the view that PKC is involved in both the induction of transf ormed morphology and the inhibition of GJIC. All the inhibitors studie d reduced PKC activity in SHE cell extracts. IC50 values were determin ed to be 0.008 mu M for staurosporine, 55 mu M for H-7 and 16 mu M for polymyxin B. The values for staurosporine and H-7 corresponded to tho se concentrations that suppressed TPA-induced cellular responses. The lack of effect of polymyxin B on whole SHE cells indicates that this c ompound does not enter the cells.