Activated MAPK proteins negatively regulate MAP2K1:MAP2K2 heterodimers by phosphorylating MAP2K1 at T292, a residue that is not present in MAP2K2. Phosphorylation of this site in MAP2K1 promotes the dephosphorylation of the MAP2K phosphorylated activation loop (AL) by an unknown mechanism, establishing a negative feedback loop that limits MAPK signaling (Catalanotti et al, 2009; Brunet et al, 1994; Xu et al, 1999). Deletion of MAP2K1 or mutation of this site prolongs MAP2K2 AL phosphorylation and MAPK activation (Catalanotti et al, 2009).
de Matos Simoes, R,
protein serine/threonine kinase activity of p-T,Y MAPK monomers and dimers [cytosol]