MOLECULAR MECHANISMS OF INSULIN: GLYCOGEN SYNTHASE

  • Soderling, Thomas, (PI)

    Project: Research project

    Description

    The objective of these studies is to delineate the molecular
    mechanism by which the phosphorylation state of skeletal muscle
    glycogen synthase is altered in diabetes and by insulin treatment.
    Emphasis will be focused on those protein kinases which
    phosphorylate sites 2 and 3 in glycogen synthase and/or activate
    the Mg++/ATP-dependent protein phosphatase I. Effects of the
    insulin receptor tyrosine protein kinase on these serine/threonine
    protein kinases and phosphatases will be examined directly using
    purified enzymes as well as in situ in diaphragm and cultured
    cells. In the latter case a highly specific antiphosphotyrosine
    monoclonal antibody affinity column will be utilized to
    selectively purify protein kinases and phosphatases containing
    phosphotyrosine. Another approach will be to assess potential
    effects of insulin-generated "modulator" molecules, derived from
    a phosphatidylinositol-glycan by activation of a specific
    phospholipase C, on these glycogen synthase protein kinases and
    phosphatases. Potential effects of insulin on the subcellular
    distribution of the protein kinase that activates the Mg /ATP-
    dependent phosphatase and on the phosphatase itself will be
    examined.
    StatusFinished
    Effective start/end date7/1/786/30/94

    Funding

    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health

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    Glycogen Synthase
    Protein Kinases
    Insulin
    Phosphoric Monoester Hydrolases
    Phosphoprotein Phosphatases
    Adenosine Triphosphate
    Phosphorylation
    Glycogen Synthase Kinases
    Glycosylphosphatidylinositols
    Antibody Affinity
    Protein-Serine-Threonine Kinases
    Receptor Protein-Tyrosine Kinases
    Phosphotransferases
    Diaphragm
    Muscles
    Enzymes
    Uridine Diphosphate Glucose
    Liver
    Cyclic Nucleotides
    Calmodulin

    ASJC

    • Medicine(all)