Activated ERK1/2 threonine-phosphorylate FRS2alpha. Authored: Rothfels, K, 2011-08-15 EC Number: 2.7.11.24 FRS2alpha has 8 canonical MAPK phosphorylation sites which are phosphorylated by activated ERK1/2 after FGF stimulation. Phosphorylation of these 8 threonine residues counteracts the activating effect of tyrosine phosphorylation of FRS2alpha, although the exact mechanism for this negative regulation is not known. Expression of a version of FRS2alpha in which the 8 threonine residues are mutated to valine results in enhanced tyrosine phosphorylation of FRS2alpha, enhanced GRB2-SOS1 recruitment and a more sustained MAPK response. The 8 threonine residues are not conserved in FRS2beta; as a result, signaling through FRS2beta complexes do not appear to be subject to this downregulation. Pubmed12419216 Pubmed12974390 Pubmed18452557 Pubmed19652666 Reactome Database ID Release 431270466 Reactome, http://www.reactome.org ReactomeREACT_111161 Reviewed: Gotoh, N, 2011-08-26 has a Stoichiometric coefficient of 8 Activated FGFR:pThr-FRS2alpha Activated FGFR:FRS2alpha