Dual role of protein kinase C on mitogen-activated protein kinase activation and human keratinocyte proliferation.

Subconfluent normal human keratinocytes exhibit autonomous (autocrine growth factor driven) proliferation and express the specific markers for keratinocyte proliferation K#5 and K#14. In keratinocyte autocrine culture, the exogenously added epidermal growth factor (EGF) has no effect on cell proliferation and mitogen-activated protein kinase (MAPK) activity. PD98059 inhibits MAPK pathway and autocrine keratinocyte proliferation. Staurosporine and Gö6976 strongly inhibit autonomous keratinocyte proliferation. In contrast, Gö6983 (which does not inhibit PKC micro ) inhibits only 20% of autocrine keratinocyte proliferation. Staurosporine inhibits MAPK activity, whereas Gö6976 and Gö6983 strongly increase it. We have concluded that MAPK, PKC micro and probably PKCalpha take part in autocrine keratinocyte proliferation. The effect of Gö6976 and Gö6983 on MAPK activity could be explained by the inhibition of PKC-dependent MAPK-phosphatase expression. The effect of staurosporine could be explained by its paradoxical action (activation) on protein kinase C (PKC) in keratinocytes.