Role of PI 3-kinase and SH-PTP2 in insulin action.
Insulin bonding to the alpha subunit of its receptor activates the tyrosine kinase of the beta subunit. This induces the tyrosine-phosphorylation of insulin receptor substrates-1 (IRS-1) and a complex formation between IRS-1 and other proteins including GRB2, SH-PTP2, Nck, and phosphoinositide (PI) 3-kinase consisting of a regulatory 85-kDa subunit and a catalytic 110-kDa subunit. We found that insulin-induced binding of the PI 3-kinase activity to IRS-1 generates the signal to activate glucose transport and membrane ruffling. In contrast, insulin-induced binding of SH-PTP2 to IRS-1 generates the signal to activate the Ras protein.
Kasuga
M
M
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000502:physiology*; D015398:Signal Transduction
C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011972:Receptor, Insulin; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases