PathwayStep4146 PathwayStep4147 PathwayStep4144 PathwayStep4145 PathwayStep4142 PathwayStep4143 PathwayStep4140 PathwayStep4141 PathwayStep4139 PathwayStep4148 PathwayStep4149 SPRY2 binds GRB2 SPRY2 translocates to the plasma membrane SRC phosphorylates SPRY2 on Y55 and Y227 PPA2A dephosphorylates SPRY2 SPRY2 binds CBL Phosphorylated SPRY2 is ubiquitinated by CBL CBL dissociates from ubiquitinated p-SPRY2 SPRY2 is phosphorylated by phosphorylated MNK1 SPRY2 is serine phosphorylated in response to MAPK activation B-RAF dissociates from S111/S120 p-SPRY2 SHP2 dephosphorylates SPRY2 Spry regulation of FGF signaling Authored: Rothfels, K, 2011-08-15 Pubmed16893902 Pubmed19570949 Pubmed19690147 Pubmed9458049 Reactome Database ID Release 431295596 Reactome, http://www.reactome.org ReactomeREACT_111080 Reviewed: Gotoh, N, 2011-08-26 Sprouty was initially characterized as a negative regulator of FGFR signaling in Drosophila. Human cells contain four genes encoding Sprouty proteins, of which Spry2 is the best studied and most widely expressed. Spry proteins modulate the duration and extent of signaling through the MAPK cascade after FGF stimulation, although the mechanism appears to depend on the particular biological context. Some studies have suggested that Sprouty binds to GRB2 and interferes with the recruitment of GRB2-SOS1 to the receptor, while others have shown that Sprouty interferes with the MAPK cascade at the level of RAF activation. In addition to modulating the MAPK pathway in response to FGF stimulation, Sprouty itself appears to be subject to complex post-translational modification that regulates its activity and stability.