Binding of Shc to the NPXY motif is mediated by its N-terminal domain.
Shc is an SH2-containing adapter protein that binds to and is phosphorylated by a large number of growth factor receptors. Phosphorylated Shc is able to interact with the Grb2-Sos complex which is responsible for mediating nucleotide exchange on Ras. We have shown previously that binding of Shc to the epidermal growth factor (EGF)-like receptor, c-ErbB-3, is through an NPXY motif (Prigent, S. A., and Gullick, W. J. (1994) EMBO J. 13, 2831-2841) shared by middle T antigen, TrkA, and EGF receptor. It has recently been reported that a region distinct from the SH2 domain is able to bind to tyrosine-phosphorylated proteins. In this paper we have used fusion proteins of various Shc domains to show that it is the N-terminal domain of Shc that is primarily responsible for binding EGF receptor and c-ErbB-3. Furthermore, by competition studies with synthetic phosphopeptides we have shown that this N-terminal domain binds to the previously identified NPXY motif.
Prigent
S A
SA
University of California, San Diego Cancer Center, La Jolla 92093-0684, USA.
Pillay
T S
TS
Ravichandran
K S
KS
Gullick
W J
WJ
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D020893:Receptor, ErbB-3; D011993:Recombinant Fusion Proteins; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D010748:Phosphopeptides; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D066246:ErbB Receptors; D020893:Receptor, ErbB-3