SPRY2 binds GRB2 Authored: Rothfels, K, 2011-08-15 Pubmed15637081 Pubmed16893902 Reactome Database ID Release 431295613 Reactome, http://www.reactome.org ReactomeREACT_111229 Reviewed: Gotoh, N, 2011-08-26 Some evidence suggests that SPRY2 may exert its negative effect by binding to GRB2 and competing with the GRB2:SOS1 interaction that is required for MAPK activation. SPRY2 phosphorylation at Y55 is stimulated in response to both FGF and EGF, and is required for SPRY2 to act as a negative regulator of FGF signaling. Y55 is not thought to be a GRB2 binding site, however. Instead, phosphorylation at Y55 is thought to cause a conformational change in SPRY2 that reveals a cryptic PXXPXPR GRB2-docking site in the C-terminal of SPRY2.<br>SPRY2 has also been shown to be phosphorylated at multiple tyrosine residues in its C-terminal in response to FGF, but not EGF, stimulation. This phosphorylation, in particular at residue 227, is thought to augment the ability of SPRY2 to inhibit FGF signaling through the MAPK cascade, although the mechanism remains to be elucidated. PPA2A (A:C):Y55/Y227 p-SPRY2:GRB2 PP2A(A:C):Y55/Y227-pSPRY2