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).
Xu, BE, Wilsbacher, JL, Collisson, T, Cobb, MH
Catalanotti, F, Reyes, G, Jesenberger, V, Galabova-Kovacs, G, de Matos Simoes, R, Carugo, O, Baccarini, M
Brunet, A, Pages, G, Pouyssegur, J
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