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Insulin signal transduction through protein kinase cascades

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Abstract

This review summarizes the evolution of ideas concerning insulin signal transduction, the current information on protein ser/thr kinase cascades as signalling intermediates, and their status as participants in insulin regulation of energy metabolism. Best characterized is the Ras-MAPK pathway, whose input is crucial to cell fate decisions, but relatively dispensable in metabolic regulation. By contrast the effectors downstream of PI-3 kinase, although less well elucidated, include elements indispensable for the insulin regulation of glucose transport, glycogen and cAMP metabolism. Considerable information has accrued on PKB/cAkt, a protein kinase that interacts directly with Ptd Ins 3′OH phosphorylated lipids, as well as some of the elements further downstream, such as glycogen synthase kinase-3 and the p70 S6 kinase. Finally, some information implicates other erk pathways (e.g. such as the SAPK/JNK pathway) and Nck/cdc42-regulated PAKs (homologs of the yeast Ste 20) as participants in the cellular response to insulin. Thus insulin recruits a broad array of protein (ser/thr) kinases in its target cells to effectuate its characteristic anabolic and anticatabolic programs.

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  1. Diabetes Unit, Medical Services and the Department of Molecular Biology, Massachusetts General Hospital, USA

    Joseph Avruch

  2. Department of Medicine, Harvard Medical School, Boston, MA, 02114, USA

    Joseph Avruch

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Avruch, J. Insulin signal transduction through protein kinase cascades. Mol Cell Biochem 182, 31–48 (1998). https://doi.org/10.1023/A:1006823109415

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