A PKC-eta/Fyn-Dependent pathway leading to keratinocyte growth arrest and differentiation

Growth control of epithelial cells differs substantially from other cell ty pes. Activation of Fyn, a Src kinase family member, is required for normal keratinocyte differentiation. We report that increased Fyn activity by itse lf suppresses growth of keratinocytes, but not dermal fibroblasts, through downmodulation of EGF receptor (EGFR) signaling. Protein kinase C-eta has a lso been implicated in keratinocyte growth/differentiation control. We show that growth suppression of keratinocytes by PKC-eta depends mostly on Fyn. PKC-eta activity is both necessary and sufficient for Fyn activation, PKC- eta and Fyn are found in association, and recombinant PKC-eta directly acti vates Fyn. Thus, our findings reveal a direct cross talk between PKC-eta an d Fyn, which presides over the decision between keratinocyte (epithelial) c ell growth and differentiation.