Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation.
The proteins Grb2-Sem-5, Shc and Sos have been implicated in the signalling pathway from tyrosine kinase receptors to Ras. Grb2-Sem-5 binds directly to murine Sos1, a Ras exchange factor, through two SH3 domains. Sos is also associated with ligand-activated tyrosine kinase receptors which bind Grb2-Sem-5, and with the Grb2-Sem-5 binding protein, Shc. Ectopic expression of Drosophila Sos stimulates morphological transformation of rodent fibroblasts. These data define a pathway by which tyrosine kinases act through Ras to control cell growth and differentiation.
Egan
S E
SE
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
Giddings
B W
BW
Brooks
M W
MW
Buday
L
L
Sizeland
A M
AM
Weinberg
R A
RA
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans; D002454:Cell Differentiation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004277:DNA, Single-Stranded; D004330:Drosophila; D066246:ErbB Receptors / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D020664:Son of Sevenless Proteins
D048868:Adaptor Proteins, Signal Transducing; D004277:DNA, Single-Stranded; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse; C495950:Grb2 protein, rat; D008565:Membrane Proteins; D011506:Proteins; D020664:Son of Sevenless Proteins; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)