IRS-1 is a common element in insulin and insulin-like growth factor-I signaling to the phosphatidylinositol 3'-kinase.
IRS-1 is a unique cytosolic protein that becomes tyrosine phosphorylated during insulin stimulation of intact cells and immediately associates with the phosphatidylinositol 3'-kinase (PtdIns 3'-kinase). The insulin-like growth factor-I (IGF-I) receptor also mediated the tyrosine phosphorylation of IRS-1 and increased the amount of PtdIns 3'-kinase activity bound to IRS-1 in Chinese hamster ovary cells. Purified insulin receptor and IGF-I receptor phosphorylated recombinant baculovirus-produced IRS-1 on similar sites in vitro, and phosphorylated baculovirus-produced IRS-1 bound PtdIns 3'-kinase activity from lysates of quiescent cells. Treatment of cells with IGF-I activated the PtdIns 3'-kinase, suggesting that IGF-I activates the PtdIns 3'-kinase through IRS-1 binding to p85 in a manner similar to insulin. Chinese hamster ovary cells overexpressing IRS-1 demonstrated increased tyrosine phosphorylation of IRS-1, and more PtdIns 3'-kinase activity associated with IRS-1 in these cells. These data demonstrate that IRS-1 is a common element for signal transmission by the IGF-I and insulin receptors.
Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215.
M G
MG
Myers
X J
XJ
Sun
B
B
Cheatham
B R
BR
Jachna
E M
EM
Glasheen
J M
JM
Backer
M F
MF
White
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin