Phosphorylated SHC1 recruits SHIP Authored: Ray, KP, 2010-05-17 Edited: Jupe, S, 2010-08-06 Pubmed10194451 Pubmed10207047 Pubmed10570274 Pubmed7898932 Pubmed9058724 Pubmed9083021 Pubmed9099679 Pubmed9108392 Pubmed9852043 Reactome Database ID Release 43913374 Reactome, http://www.reactome.org ReactomeREACT_23874 Reviewed: Dooms, H, 2011-03-17 Reviewed: Villarino, A, 2011-02-11 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). has a Stoichiometric coefficient of 4 SHIP1,2 Interleukin receptor complexes with activated SHC1 Interleukin receptor complexes with activated SHC1:SHIP1,2