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).
Jesenberger, V, de Matos Simoes, R, Galabova-Kovacs, G, Baccarini, M, Reyes, G, Carugo, O, Catalanotti, F
Cobb, MH, Wilsbacher, JL, Xu, BE, Collisson, T
Brunet, A, Pouyssegur, J, Pages, G
protein serine/threonine kinase activity of p-T,Y MAPK monomers and dimers [cytosol]
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