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

Morag Shaw, Philip Cohen (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    79 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)120-124
    Number of pages5
    JournalFEBS Letters
    Volume461
    Issue number1-2
    DOIs
    Publication statusPublished - 12 Nov 1999

    Keywords

    • Epidermal growth factor
    • Glycogen synthase kinase 3
    • Insulin
    • MAP kinase
    • Protein kinase B

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