Several studies suggest that the tyrosine-specific protein kinase activity of the β-subunit of the insulin receptor is necessary to mediate the biological effects of insulin. This conclusion leads to the hypothesis that the effect of insulin is mediated through the tyrosine phosphorylation of cellular substrates by the insulin-receptor tyrosine kinase. In this review, the experimental evidence regarding insulin-stimulated phosphorylation of proteins both in vitro and in vivo is evaluated. In a cell-free system, tubulin, microtubuleassociated protein 2, tau, fodrin, calmodulin-dependent kinase, calmodulin, and lipocortins 1 and 2 were reported to be good substrates for insulin-receptor kinase. However, none were found to be tyrosine phosphorylated in an intact-cell system. In intact-cell systems, proteins of M, 185,000 (pp185), 120,000 (pp120), 240,000 (pp240), 15,000 (pp15), 60,000 (pp60), and 62,000 (pp62) as well as several others were reported to be tyrosine phosphorylated in an insulin-dependent fashion. However, the function or functional alteration of these proteins induced by insulin-stimulated tyrosine phosphorylation is not clear. Therefore, physiologically relevant substrates for the insulin-receptor kinase have not been established, and more work is necessary to verify the phosphorylation cascade hypothesis of insulin action.
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Original Articles|
March 01 1990
Substrates for Insulin-Receptor Kinase
Masato Kasuga, MD;
Masato Kasuga, MD
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo, Japan
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Tetsuro Izumi, MD;
Tetsuro Izumi, MD
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo, Japan
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Kazuyuki Tobe, MD;
Kazuyuki Tobe, MD
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo, Japan
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Teruo Shiba, MD;
Teruo Shiba, MD
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo, Japan
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Kaoru Momomura, PhD;
Kaoru Momomura, PhD
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo, Japan
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Yuko Tashiro-Hashimoto, PhD;
Yuko Tashiro-Hashimoto, PhD
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo, Japan
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Takashi Kadowaki, MD
Takashi Kadowaki, MD
Department of Internal Medicine, Faculty of Medicine, University of Tokyo
Tokyo, Japan
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Address correspondence and reprint requests to Dr. Masato Kasuga, The Third Department of Internal Medicine, University of Tokyo, 7–3-1 Hongo, Bunkyoku, Tokyo, Japan 113.
Citation
Masato Kasuga, Tetsuro Izumi, Kazuyuki Tobe, Teruo Shiba, Kaoru Momomura, Yuko Tashiro-Hashimoto, Takashi Kadowaki; Substrates for Insulin-Receptor Kinase. Diabetes Care 1 March 1990; 13 (3): 317–326. https://doi.org/10.2337/diacare.13.3.317
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