Insulin signal transduction through protein kinase cascades

• Published in: Molecular and cellular biochemistry 1998-05, Vol.182 (1-2), p.31-48
• Main Author: Avruch, J
• Format: Article
• Language: English
• Subjects: Animals; Humans; Insulin; Insulin - metabolism; Insulin - physiology; Kinases; Lipids; Models, Biological; Protein-Serine-Threonine Kinases - metabolism; Protein-Serine-Threonine Kinases - physiology; Proteins; Signal transduction; Signal Transduction - physiology; Yeasts
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1023/A:1006823109415

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.