SOS1 activates H-Ras Phosphorylated SHC1 recruits SHIP Phosphorylated SHC1 recruits GRB2:GAB2 SHC1 mediates cytokine-induced phosphorylation of GAB2 Gab2 binds the p85 subunit of Class 1A PI3 kinases Phosphorylated SHC recruits GRB2:SOS1 The SHC1:SHIP1 complex is stabilized by GRB2 PathwayStep7143 PathwayStep7144 PathwayStep7145 PathwayStep7146 PathwayStep7147 PathwayStep7148 PathwayStep7149 Interleukin receptor SHC signaling Authored: Ray, KP, 2010-05-17 Edited: Jupe, S, 2010-08-06 Phosphorylation of Shc at three tyrosine residues, 239, 240 (Gotoh et al. 1996) and 317 (Salcini et al. 1994) involves unidentified tyrosine kinases presumed to be part of the activated receptor complex. These phosphorylated tyrosines subsequently bind SH2 signaling proteins such as Grb2, Gab2 and SHIP that are involved in the regulation of different signaling pathways. Grb2 can associate with the guanosine diphosphate-guanosine triphosphate exchange factor Sos1, leading to Ras activation and regulation of cell proliferation. Downstream signals are mediated via the Raf-MEK-Erk pathway.Grb2 can also associate through Gab2 with PI3K and with SHIP.<br><br>Figure reproduced from Gu, H. et al. 2000. Mol. Cell. Biol. 20(19):7109-7120<br>Copyright American Society for Microbiology. All Rights Reserved. Pubmed10982827 Pubmed8084588 Pubmed8294403 Pubmed8947042 Reactome Database ID Release 43912526 Reactome, http://www.reactome.org ReactomeREACT_23891 Reviewed: Dooms, H, 2011-03-17 Reviewed: Villarino, A, 2011-02-11