1shc
SHC PTB DOMAIN COMPLEXED WITH A TRKA RECEPTOR PHOSPHOPEPTIDE, NMR, MINIMIZED AVERAGE STRUCTURESHC PTB DOMAIN COMPLEXED WITH A TRKA RECEPTOR PHOSPHOPEPTIDE, NMR, MINIMIZED AVERAGE STRUCTURE
Structural highlights
FunctionSHC1_HUMAN Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe nuclear magnetic resonance structure of the phosphotyrosine binding (PTB) domain of Shc complexed to a phosphopeptide reveals an alternative means of recognizing tyrosine-phosphorylated proteins. Unlike in SH2 domains, the phosphopeptide forms an antiparallel beta-strand with a beta-sheet of the protein, interacts with a hydrophobic pocket through the (pY-5) residue, and adopts a beta-turn. The PTB domain is structurally similar to pleckstrin homology domains (a beta-sandwich capped by an alpha-helix) and binds to acidic phospholipids, suggesting a possible role in membrane localization. Structure and ligand recognition of the phosphotyrosine binding domain of Shc.,Zhou MM, Ravichandran KS, Olejniczak EF, Petros AM, Meadows RP, Sattler M, Harlan JE, Wade WS, Burakoff SJ, Fesik SW Nature. 1995 Dec 7;378(6557):584-92. PMID:8524391[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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