Role of protein kinase B and the MAP kinase cascade in mediating the EGF-dependent inhibition of glycogen synthase kinase 3 in Swiss 3T3 cells

Epidermal growth factor (EGF), insulin-like growth factor 1 (IGF1) and phorbol myristate acetate (PMA) induce the inhibition of glycogen synthase kinase 3 (GSK3) by stimulating the phosphorylation of an N-terminal serine, Here, we show that protein kinase B (PKB) plays a kev role in mediating EGF-induced inhibition of GSK3 alpha and that the classical MAP kinase (MAPK) cascade has two functions in this process. Firstly, it makes a transient contribution to EGF-induced inhibition of GSK3 alpha. Secondly, it shortens the duration of PKB activation and GSK3 alpha inhibition. In contrast, PKB alone mediates the IGF1-induced inhibition of GSK3 alpha, while the MAPK cascade mediates the inhibition of GSK3a by PMA. (C) 1999 Federation of European Biochemical Societies.