c-FOS activation by phospho ERK1/2 Authored: Shamovsky, V, 2009-12-16 EC Number: 2.7.11 Edited: Shamovsky, V, 2010-02-27 Pubmed12134156 Pubmed7588633 Reactome Database ID Release 43450325 Reactome, http://www.reactome.org ReactomeREACT_21251 Reviewed: Gillespie, ME, 2010-02-27 The Fos proteins(c-Fos, FosB, Fra1 and Fra2), which cannot homodimerize, form stable heterodimers with Jun proteins and thereby enhance their DNA binding activity. <p>On activation of the MAPK pathway, Ser-374 of Fos is phosphorylated by ERK1/2 and Ser-362 is phosphorylated by RSK1/2, the latter kinases being activated by ERK1/2. If stimulation of the MAPK pathway is sufficiently sustained, ERK1/2 can dock on an upstream FTYP amino acid motif, called the DEF domain (docking site for ERKs, FXFP), and phosphorylate Thr-331 and Thr-325.</p><p>Phosphorylation at specific sites enhances the transactivating potential of several AP-1 proteins, including Jun and Fos, without having any effect on their DNA binding activities. Thus, phosphorylation of Ser-362 and Ser-374 stabilizes c-Fos but has no demonstrated role in the control of transcriptional activity. On the contrary, phosphorylation of Thr-325 and Thr-331 enhances c-Fos transcriptional activity but has no demonstrated effect on protein turnover. has a Stoichiometric coefficient of 4