Insulin signal transduction through protein kinase cascades.
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.
Avruch
J
J
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
D000818:Animals; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D007328:Insulin; D017346:Protein Serine-Threonine Kinases