Binding of the Ras activator son of sevenless to insulin receptor substrate-1 signaling complexes.
Signal transmission by insulin involves tyrosine phosphorylation of a major insulin receptor substrate (IRS-1) and exchange of Ras-bound guanosine diphosphate for guanosine triphosphate. Proteins containing Src homology 2 and 3 (SH2 and SH3) domains, such as the p85 regulatory subunit of phosphatidylinositol-3 kinase and growth factor receptor-bound protein 2 (GRB2), bind tyrosine phosphate sites on IRS-1 through their SH2 regions. Such complexes in COS cells were found to contain the heterologously expressed putative guanine nucleotide exchange factor encoded by the Drosophila son of sevenless gene (dSos). Thus, GRB2, p85, or other proteins with SH2-SH3 adapter sequences may link Sos proteins to IRS-1 signaling complexes as part of the mechanism by which insulin activates Ras.
Baltensperger
K
K
Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605.
Kozma
L M
LM
Cherniack
A D
AD
Klarlund
J K
JK
Chawla
A
A
Banerjee
U
U
Czech
M P
MP
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D051380:GRB2 Adaptor Protein; D006160:Guanosine Triphosphate / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D020664:Son of Sevenless Proteins; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D011506:Proteins; D020664:Son of Sevenless Proteins; D014443:Tyrosine; D006160:Guanosine Triphosphate; D010770:Phosphotransferases; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D016283:Proto-Oncogene Proteins p21(ras)