A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosine-binding domains is related to Shc and is specifically expressed in the brain.
The Shc adaptor protein, hereafter referred to as ShcA, possesses two distinct phosphotyrosine-recognition modules, a C-terminal Src homology 2 (SH2) domain and an N-terminal phosphotyrosine-binding (PTB) domain, and is itself phosphorylated on tyrosine in response to many extracellular signals. Phosphorylation of human ShcA at Tyr-317 within its central (CH1) region induces binding to the Grb2 SH2 domain and is thereby implicated in activation of the Ras pathway. Two shc-related genes (shcB and shcC) have been identified in the mouse. shcB is closely related to human SCK, while shcC has not yet been found in other organisms. The ShcC protein is predicted to have a C-terminal SH2 domain, a CH1 region with a putative Grb2-binding site, and an N-terminal PTB domain. The ShcC and ShcB SH2 domains bind phosphotyrosine-containing peptides and receptors with a specificity related to, but distinct from, that of the ShcA SH2 domain. The ShcC PTB domain specifically associates in vitro with the autophosphorylated receptors for nerve growth factor and epidermal growth factor. These results indicate that ShcC has functional SH2 and PTB; domains. In contrast to shcA, which is widely expressed, shcC RNA and proteins are predominantly expressed in the adult brain. These results suggest that ShcC may mediate signaling from tyrosine kinases in the nervous system, such as receptors for neurotrophins.
O'Bryan
J P
JP
Department of Pharmocology, University of North Carolina, Chapel Hill 27599, USA.
Songyang
Z
Z
Cantley
L
L
Der
C J
CJ
Pawson
T
T
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D017931:DNA Primers; D004330:Drosophila / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000737:chemistry; D009479:Neuropeptides; D009928:Organ Specificity; D010766:Phosphorylation; D019000:Phosphotyrosine; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D055765:Shc Signaling Adaptor Proteins; D000071426:Src Homology 2 Domain-Containing, Transforming Protein 2; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D011506:Proteins; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; C099021:SHC2 protein, human; C122029:SHC3 protein, human; D055765:Shc Signaling Adaptor Proteins; C486295:Shc2 protein, mouse; C485682:Shc3 protein, mouse; D000071426:Src Homology 2 Domain-Containing, Transforming Protein 2; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3; D019000:Phosphotyrosine; D066246:ErbB Receptors