Mechanisms regulating phosphoinositide 3-kinase signalling in insulin-sensitive tissues.
A great deal of evidence has accumulated indicating that the activity of PI 3-kinase is necessary, and in some cases sufficient, for a wide range of insulin's actions in the cell. Most biochemical, genetic and pharmacological studies have focused on identifying potential roles for the class-Ia PI 3-kinases which are rapidly activated following insulin stimulation. However, recent evidence indicates the alpha isoform of class-II PI 3-kinase (PI3K-C2alpha) may also play a role as insulin causes a very rapid activation of this as well. The basic mechanisms by which insulin activates the various members of the PI 3-kinase family are increasingly well understood and these studies reveal multiple mechanisms for modulating the activity and functionality of PI 3-kinase and for down regulating the signals they generate. These include inhibitory phosphorylation events, lipid phosphatases such as PTEN and SHIP2 and inhibitor proteins of the suppressors of cytokine signalling (SOCS) family. The current review will focus on these mechanisms and how defects in these might contribute to the development of insulin resistance.
Shepherd
P R
PR
Department of Biochemistry and Molecular Biology, University College London, Gower St, London WC1E 6BT, UK.
D001786:Blood Glucose / Q000032:analysis; D058541:Class II Phosphatidylinositol 3-Kinases; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology; D008055:Lipids / Q000097:blood; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D001786:Blood Glucose; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D008055:Lipids; D010750:Phosphoproteins; D012097:Repressor Proteins; D019869:Phosphatidylinositol 3-Kinases; D058541:Class II Phosphatidylinositol 3-Kinases; D005947:Glucose