SPRY2 is serine phosphorylated in response to MAPK activation Authored: Rothfels, K, 2011-08-15 Pubmed11698404 Pubmed19690147 Reactome Database ID Release 431295634 Reactome, http://www.reactome.org ReactomeREACT_111121 Reviewed: Gotoh, N, 2011-08-26 Some evidence suggests that SPRY2 can exert its negative role on FGF signaling at the level of RAF activation. Hypophosphorylated SPRY2 binds to inactive B-RAF, preventing it from activating ERK signaling. MAPK activation results in phosphorylation of SPRY2 on six serine residues (S7, S42, S111, S120, S140 and S167), and inhibits B-RAF binding. Phosphorylation at S111 and S120 directly affects B-RAF binding while the remaining four sites appear to contribute indirectly. Oncogenic forms of B-RAF such as B-RAF V600E, which adopt active kinase conformations, do not associate with SPRY2, regardless of its phosphorylation status. This suggests that two mechanisms affect the SPRY2:B-RAF interaction: SPRY2 phosphorylation and B-RAF conformation. S111/S120 p-SPRY2:B-RAF SPRY2:B-RAF