Protein phosphorylation and hormone action

P. Cohen, J. F. Antoniw, H. G. Nimmo, S. J. Yeaman

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    Although the scheme hormone → raised cyclic AMP levels → activated protein kinase → phosphorylated protein → physiological response may represent an outline for the action of several hormones, in the best understood example, namely regulation of glucogen metabolism in mammalian muscle, the picture is more complex. Modification of phosphorylase kinase by cyclic AMP dependent protein kinase, after stimulation by adrenaline, leads to phosphorylation of the enzyme at two sites. Activation is associated exclusively with the phosphorylation of the primary site, but the secondary phosphorylation indirectly antagonizes the primary phosphorylation in that it is necessary to render the primary site susceptible to dephosphorylation. The recent separation of two distinct phosphorylase kinase phosphatases specific for the two sites shows that reversal of the hormonal stimulation is controlled by the relative activities of two enzymes with opposing functions. Glycogen synthetase, which is phosphorylated and inactivated by cyclic AMP dependent protein kinase, is also under the control of insulin. Although insulin appears to stimulate glycogen synthetase by reversal of the inactivation catalysed by the cyclic AMP dependent protein kinase, tissue cyclic AMP concentrations do not alter. The recent identification of a second glycogen synthetase kinase, unaffected by cyclic AMP, therefore raises the possibility that insulin action may also be mediated through phosphorylation dephosphorylation mechanisms, which antagonize those mediated through cyclic AMP dependent protein kinase.

    Original languageEnglish
    Pages (from-to)281-295
    Number of pages15
    JournalCiba Foundation Symposium
    VolumeNo.41
    Publication statusPublished - 1976

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    Cyclic AMP-Dependent Protein Kinases
    Glycogen Synthase
    Phosphorylation
    Hormones
    Cyclic AMP
    Insulin
    Proteins
    Phosphorylase Kinase
    AMP-Activated Protein Kinases
    Enzymes
    Epinephrine
    Phosphotransferases
    Muscles

    Cite this

    Cohen, P., Antoniw, J. F., Nimmo, H. G., & Yeaman, S. J. (1976). Protein phosphorylation and hormone action. Ciba Foundation Symposium, No.41, 281-295.
    Cohen, P. ; Antoniw, J. F. ; Nimmo, H. G. ; Yeaman, S. J. / Protein phosphorylation and hormone action. In: Ciba Foundation Symposium. 1976 ; Vol. No.41. pp. 281-295.
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    abstract = "Although the scheme hormone → raised cyclic AMP levels → activated protein kinase → phosphorylated protein → physiological response may represent an outline for the action of several hormones, in the best understood example, namely regulation of glucogen metabolism in mammalian muscle, the picture is more complex. Modification of phosphorylase kinase by cyclic AMP dependent protein kinase, after stimulation by adrenaline, leads to phosphorylation of the enzyme at two sites. Activation is associated exclusively with the phosphorylation of the primary site, but the secondary phosphorylation indirectly antagonizes the primary phosphorylation in that it is necessary to render the primary site susceptible to dephosphorylation. The recent separation of two distinct phosphorylase kinase phosphatases specific for the two sites shows that reversal of the hormonal stimulation is controlled by the relative activities of two enzymes with opposing functions. Glycogen synthetase, which is phosphorylated and inactivated by cyclic AMP dependent protein kinase, is also under the control of insulin. Although insulin appears to stimulate glycogen synthetase by reversal of the inactivation catalysed by the cyclic AMP dependent protein kinase, tissue cyclic AMP concentrations do not alter. The recent identification of a second glycogen synthetase kinase, unaffected by cyclic AMP, therefore raises the possibility that insulin action may also be mediated through phosphorylation dephosphorylation mechanisms, which antagonize those mediated through cyclic AMP dependent protein kinase.",
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    Cohen, P, Antoniw, JF, Nimmo, HG & Yeaman, SJ 1976, 'Protein phosphorylation and hormone action', Ciba Foundation Symposium, vol. No.41, pp. 281-295.

    Protein phosphorylation and hormone action. / Cohen, P.; Antoniw, J. F.; Nimmo, H. G.; Yeaman, S. J.

    In: Ciba Foundation Symposium, Vol. No.41, 1976, p. 281-295.

    Research output: Contribution to journalArticle

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    Cohen P, Antoniw JF, Nimmo HG, Yeaman SJ. Protein phosphorylation and hormone action. Ciba Foundation Symposium. 1976;No.41:281-295.