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Studies on the Regulation of Glycogen and Lipid Metabolism by Insulin and Growth Factors: The Involvement of Receptor Tyrosine Kinase Activation and Casein Kinase II

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Molecular Mechanisms of Hormone Action

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Abstract

One of the fundamental questions today in studies on the regulation of glycogen and lipid metabolism by insulin and the growth factors whose receptors are protein tyrosine kinases, is how do these ligands on binding to their respective receptors communicate responses to the cytoplasm. Initial events in signaling begin with increased autophosphorylation on tyrosine and serine residues of the cytoplasmic domains of the receptors themselves. Indeed, it is now generally accepted that binding of these hormones results in the activation of intrinsic tyrosine kinase activity, and that this activity is prerequisite and essential for all subsequent metabolic events (for reviews, see Denton 1986; Rosen 1987; Pelech et al. 1987; Czech et al. 1988). These immediate events bring about both increases and decreases in the phosphorylation state (on serine and threonine residues) of many of the important regulatory proteins and enzymes of protein synthesis, glycogen and lipid metabolism, e.g., ribosomal protein S6, glycogen synthase, pyruvate-dehydrogenase, ATP-citrate lyase, acetyl-CoA carboxylase, hormone-sensitive lipase. Importantly, in some instances, good evidence has been obtained to show that these effects on phosphorylation correlate well with changes in the flux of substrates through each respective pathway and also with changes in the intrinsic activity of the individual regulatory steps concerned (for reviews, see Strålfors et al. 1984; Cohen 1986; Roach 1986; Denton 1986).

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Authors and Affiliations

  1. The Howard Hughes Medical Institute, University of Washington, Seattle, WA, 98195, USA

    T. A. J. Haystead & E. G. Krebs

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  1. T. A. J. Haystead
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  2. E. G. Krebs
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Editors and Affiliations

  1. Institut für Biologische Chemie, Universität Heidelberg, Im Neuenheimer Feld 510, 6900, Heidelberg, Germany

    Ulrich Gehring

  2. Institut für Physiologische Chemie, Universität Würzburg, Koellikerstr. 2, 8700, Würzburg, Germany

    Ernst J. M. Helmreich

  3. Institut für Pharmakologie, Freie Universität Berlin, Thielallee 67-73, 1000, Berlin 33, Germany

    Günter Schultz

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© 1989 Springer-Verlag Berlin Heidelberg

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Haystead, T.A.J., Krebs, E.G. (1989). Studies on the Regulation of Glycogen and Lipid Metabolism by Insulin and Growth Factors: The Involvement of Receptor Tyrosine Kinase Activation and Casein Kinase II. In: Gehring, U., Helmreich, E.J.M., Schultz, G. (eds) Molecular Mechanisms of Hormone Action. 40. Colloquium der Gesellschaft für Biologische Chemie 6.– 8. April 1989 in Mosbach/Baden, vol 40. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75022-9_8

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  • DOI: https://doi.org/10.1007/978-3-642-75022-9_8

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