Phosphorylated SHC1 recruits SHIP

Stable Identifier
R-HSA-913374
Type
Reaction [binding]
Species
Homo sapiens
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SHIP dephosphorylates PIP3 and may limit the magnitude or duration of signaling events that are dependent upon PIP3-mediated membrane recruitment of plextrin homology (PH) domain signalling proteins such as PI3K and Akt (Aman et al. 1998). The PTB domain of SHC1 binds to phosphorylated tyrosine residues on SHIP. Mutations that inactivate the PTB domain prevent this binding and substitution of F for Y917 and Y1020 on SHIP prevents creation of the phosphotyrosine motifs that are recognized by the SHC1 PTB domain, blocking the interaction (Lamkin et al. 1997). A functional SHIP SH2 domain is also reported as a requirement for association of SHIP with Shc (Liu et al. 1997). GRB2 stabilizes the SHC1/SHIP complex (Harmer & DeFranco 1999), presumably by simultaneously binding via its SH3 domains to SHIP and via its SH2 domain to phosphotyrosines on SHC1, forming a ternary complex of SHC1:GRB2:SHIP described as inducible by IL-3, IL-5 or GM-CSF by many authors (Jucker et al. 1997, Lafrancone et al. 1995, Odai et al. 1997). SHIP2 also associates with SHC1 but does not appear to require Grb2 for stability (Wisniewskiet al. 1999).

Literature References
PubMed ID Title Journal Year
9099679 Shc interaction with Src homology 2 domain containing inositol phosphatase (SHIP) in vivo requires the Shc-phosphotyrosine binding domain and two specific phosphotyrosines on SHIP

Lamkin, TD, Walk, SF, Liu, L, Damen, JE, Krystal, G, Ravichandran, KS

J Biol Chem 1997
9108392 Purification and molecular cloning of SH2- and SH3-containing inositol polyphosphate-5-phosphatase, which is involved in the signaling pathway of granulocyte-macrophage colony-stimulating factor, erythropoietin, and Bcr-Abl

Odai, H, Sasaki, K, Iwamatsu, A, Nakamoto, T, Ueno, H, Yamagata, T, Mitani, K, Yazaki, Y, Hirai, H

Blood 1997
10570274 Tyrosine phosphorylation of shc in response to B cell antigen receptor engagement depends on the SHIP inositol phosphatase

Ingham, RJ, Okada, H, Dang-Lawson, M, Dinglasan, J, van der Geer, P, Kurosaki, T, Gold, MR

J Immunol 1999
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