Insulin signal transduction through protein kinase cascades

  • Joseph Avruch
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 24)


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. (Mol Cell Biochem 182: 31-48, 1998)

Key words

insulin action protein serine/threonine kinase Ras-Raf MAP kinase ribosomal S6 protein kinase (RSKs) phosphatidyl inositol-3 kinase 


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Copyright information

© Springer Science+Business Media Dordrecht 1998

Authors and Affiliations

  • Joseph Avruch
    • 1
  1. 1.Diabetes Unit, Medical Services and the Department of Molecular Biology, Massachusetts General Hospital, and the Department of MedicineHarvard Medical SchoolBostonUSA

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