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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 1
Author(s) -
Shaw Morag,
Cohen Philip
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)01434-9
Subject(s) - gsk 3 , glycogen synthase , map kinase kinase kinase , protein kinase b , mitogen activated protein kinase kinase , epidermal growth factor , mapk/erk pathway , chemistry , protein kinase c , map2k7 , protein kinase a , c raf , kinase , phosphorylation , microbiology and biotechnology , cyclin dependent kinase 2 , biology , biochemistry , receptor
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 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.