scholarly journals Grb10 Interacts Differentially with the Insulin Receptor, Insulin-like Growth Factor I Receptor, and Epidermal Growth Factor Receptor via the Grb10 Src Homology 2 (SH2) Domain and a Second Novel Domain Located between the Pleckstrin Homology and SH2 Domains

1998 ◽  
Vol 273 (12) ◽  
pp. 6860-6867 ◽  
Author(s):  
Weimin He ◽  
David W. Rose ◽  
Jerrold M. Olefsky ◽  
Thomas A. Gustafson
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Sh2 Domain ◽  
Sh2 Domains ◽  
Factor I ◽  
Src Homology 2 ◽  
Src Homology ◽  
Epidermal Growth

scholarly journals The phosphotyrosine interaction domain of Shc binds an LXNPXY motif on the epidermal growth factor receptor.

1995 ◽  
Vol 15 (8) ◽  
pp. 4403-4409 ◽  
Author(s):  
A G Batzer ◽  
P Blaikie ◽  
K Nelson ◽  
J Schlessinger ◽  
B Margolis
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Sh2 Domain ◽  
Interaction Domain ◽  
Competition Analysis ◽  
Amino Terminal ◽  
Epidermal Growth ◽  
Domain Protein

Shc is an SH2 domain protein that is tyrosine phosphorylated in cells stimulated with a variety of growth factors and cytokines. Once phosphorylated, Shc binds the Grb2-Sos complex, leading to Ras activation. Shc can interact with tyrosine-phosphorylated proteins by binding to phosphotyrosine in the context of an NPXpY motif, where pY is a phosphotyrosine. This is an unusual binding site for an SH2 domain protein whose binding specificity is usually controlled by residues carboxy terminal, not amino terminal, to the phosphotyrosine. Recently we identified a second region in Shc, named the phosphotyrosine interaction (PI) domain, and we have found it to be present in a variety of other cellular proteins. In this study we used a dephosphorylation protection assay, competition analysis with phosphotyrosine-containing synthetic peptides, and epidermal growth factor receptor (EGFR) mutants to determine the binding sites of the PI domain of Shc on the EGFR. We demonstrate that the PI domain of Shc binds the LXNPXpY motif that encompasses Y-1148 of the activated EGFR. We conclude that the PI domain imparts to Shc its ability to bind the NPXpY motif.

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