A region in Shc distinct from the SH2 domain can bind tyrosine-phosphorylated growth factor receptors.
Shc is a ubiquitously expressed Src homology 2 (SH2) domain protein that can transform fibroblasts and differentiate PC12 cells in a Ras-dependent fashion. Shc binds a variety of tyrosine-phosphorylated growth factor receptors presumably via its carboxyl-terminal SH2 domain. We cloned a fragment of Shc when screening a bacterial expression library with tyrosine-phosphorylated epidermal growth factor (EGF) receptor. Surprisingly, this fragment encodes the amino terminus of Shc, a region that has no significant similarity to an SH2 domain. When expressed as a glutathione S-transferase fusion protein, this amino-terminal domain binds to autophosphorylated EGF receptor, as well as HER2/neu and TrkA receptors. This fragment acts like an SH2 domain in that it does not bind non-phosphorylated EGF receptor or EGF receptor with all tyrosine phosphorylation sites mutated or deleted. Our data define a novel domain in Shc that has the potential to interact with growth factor receptors and other tyrosine-phosphorylated proteins.
Blaikie
P
P
Department of Pharmacology, New York University Medical Center, New York 10016.
Immanuel
D
D
Wu
J
J
Li
N
N
Yajnik
V
V
Margolis
B
B
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017978:Receptors, Growth Factor / Q000378:metabolism*; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D011506:Proteins; D017978:Receptors, Growth Factor; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine; D018631:ras Proteins