Epidermal growth factor stimulates the tyrosine phosphorylation of SHC in the mouse.
Previous studies have demonstrated that the administration of epidermal growth factor (EGF) to neonatal mice results in the tyrosine phosphorylation of multiple substrates in all organs examined (Donaldson, R. W., and Cohen, S. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 8477-8481). One of these substrates, a 55-kDa protein, was shown to associate with the receptor for EGF (EGFR). We now report the identification of this receptor-associated protein as SHC. Immunoprecipitation and Western blotting analyses have revealed that SHC associates only with the activated EGFR. In the absence of EGF stimulation, SHC exists in the liver as a cytoplasmic monomer. Intraperitoneal injection of EGF results, within minutes, in the translocation of 50-80% of SHC to the liver plasma membrane. The membrane-associated SHC was found to be tyrosine-phosphorylated; the subsequent release of SHC from the membrane correlated with a tyrosine dephosphorylation. We conclude that SHC is a physiological substrate that appears to participate in the in vivo signaling response to EGF.
Ruff-Jamison
S
S
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
McGlade
J
J
Pawson
T
T
Chen
K
K
Cohen
S
S
D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011485:Protein Binding; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D002352:Carrier Proteins; D010750:Phosphoproteins; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors