MAPKAP kinase-2; a novel protein kinase activated by mitogen-activated protein kinase

D. Stokoe, D. G. Campbell, S. Nakielny, H. Hidaka, S. J. Leevers, C. Marshall, P. Cohen

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    381 Citations (Scopus)

    Abstract

    A novel protein kinase, which was only active when phosphorylated by the mitogen-activated protein kinase (MAP kinase), has been purified 85 000-fold to homogeneity from rabbit skeletal muscle. This MAP kinase activated protein kinase, termed MAPKAP kinase-2, was distinguished from S6 kinase-II (MAPKAP kinase-1) by its response to inhibitors, lack of phosphorylation of S6 peptides and amino acid sequence. MAPKAP kinase-2 phosphorylated glycogen synthase at Ser7 and the equivalent serine (*) in the peptide KKPL NRTLS(*)VASLPGLamide whose sequence is similar to the N terminus of glycogen synthase. MAPKAP kinase-2 was resolved into two monomeric species of apparent molecular mass 60 and 53kDa that had similar specific activities and substrate specificities. Peptide sequences of the 60 and 53kDa species were identical, indicating that they are either closely related isoforms or derived from the same gene. MAP kinase activated the 60 and 53kDa forms of MAPKAP kinase-2 by phosphorylating the first threonine residue in the sequence VPQTPLHTSR. Furthermore, Mono Q chromatography of extracts from rat phaeochromocytoma and skeletal muscle demonstrated that two MAP kinase isoforms (p42(mapk) and p44(mapk)) were the only enzymes in these cells that were capable of reactivating MAPKAP kinase-2. These results indicate that MAP kinase activates at least two distinct protein kinases, suggesting that it represents a point at which the growth factor-stimulated protein kinase cascade bifurcates.

    Original languageEnglish
    Pages (from-to)3985-3994
    Number of pages10
    JournalEMBO Journal
    Volume11
    Issue number11
    Publication statusPublished - 1992

    Keywords

    • Growth factors
    • MAP kinase
    • Protein kinase
    • Protein phosphorylation

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