Role of protein kinase B and the MAP kinase cascade in mediating the EGF-dependent inhibition of glycogen synthase kinase 3 in Swiss 3T3 cells11This paper is dedicated to the memory of Dr. Yuji Saito who initiated work in our laboratory on the regulation of GSK3 by EGF.

AbstractEpidermal 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 key role in mediating EGF-induced inhibition of GSK3α 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 GSK3α. Secondly, it shortens the duration of PKB activation and GSK3α inhibition. In contrast, PKB alone mediates the IGF1-induced inhibition of GSK3α, while the MAPK cascade mediates the inhibition of GSK3α by PMA