Phorbol ester effects in atypical protein kinase C zeta overexpressing NIH3T3 cells: Possible evidence for crosstalk between protein kinase C isoforms

To examine whether multiple protein kinase C (PKC) isoforms could interact or crosstalk, phorbol ester-insensitive atypical PKC (aPKC) zeta isoform was overexpressed in NIH3T3 cells, and the cells were stimulated with phorbol ester to activate diacylglycerol-dependent conventional (cPKC) and novel PKC (nPKC) isoforms. Treatment of cells with phorbol ester which activates PKC alpha, gamma, delta, and epsilon isoforms in NIH3T3 cells significantly reduced proliferation of cells. Over-expression of aPKC zeta and subsequent phorbol ester treatment abolished phorbol ester-induced reduction in cell proliferation. Overexpression of aPKC zeta also potentiated phorbol ester-induced mitogen-activated protein (MAP) kinase activation in a PKC-dependent manner. The effects of PKC zeta overexpression on proliferation and MAP kinase activation were proportional to the levels of aPKC zeta expression. Since aPKC zeta cannot be activated by phorbol ester, modulation of cell proliferation and MAP kinase activation by phorbol ester in aPKC zeta overexpressing cells might be due to the activation of cPKCs and/or nPKCs by phorbol ester. Thus, the results provide possible evidence for either direct or indirect crosstalk between PKC isoforms. (C) 1997 Academic Press.