Activated MAPKs phosphorylate MAP2K1

Stable Identifier
R-HSA-5674496
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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Activated MAPKs phosphorylate MAP2K1
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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).
Literature References
PubMed ID Title Journal Year
19219045 A Mek1-Mek2 heterodimer determines the strength and duration of the Erk signal

Jesenberger, V, de Matos Simoes, R, Galabova-Kovacs, G, Baccarini, M, Reyes, G, Carugo, O, Catalanotti, F

Nat. Struct. Mol. Biol. 2009
10567369 The N-terminal ERK-binding site of MEK1 is required for efficient feedback phosphorylation by ERK2 in vitro and ERK activation in vivo

Cobb, MH, Wilsbacher, JL, Xu, BE, Collisson, T

J. Biol. Chem. 1999
8013650 Growth factor-stimulated MAP kinase induces rapid retrophosphorylation and inhibition of MAP kinase kinase (MEK1)

Brunet, A, Pouyssegur, J, Pages, G

FEBS Lett 1994
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Output
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as an event of
Catalyst Activity

protein serine/threonine kinase activity of p-T,Y MAPK monomers and dimers [cytosol]

Physical Entity
p-T,Y MAPK monomers and dimers [cytosol] (Homo sapiens)
Activity
protein serine/threonine kinase activity (GO:0004674)
Orthologous Events
Activated MAPKs phosphorylate MAP2K1 (Bos taurus)
Activated MAPKs phosphorylate MAP2K1 (Caenorhabditis elegans)
Activated MAPKs phosphorylate MAP2K1 (Danio rerio)
Activated MAPKs phosphorylate MAP2K1 (Dictyostelium discoideum)
Activated MAPKs phosphorylate MAP2K1 (Drosophila melanogaster)
Activated MAPKs phosphorylate MAP2K1 (Mus musculus)
Activated MAPKs phosphorylate MAP2K1 (Rattus norvegicus)
Activated MAPKs phosphorylate MAP2K1 (Saccharomyces cerevisiae)
Activated MAPKs phosphorylate MAP2K1 (Schizosaccharomyces pombe)
Authored
Rothfels, K  (2015-02-12)
Reviewed
Roskoski, R Jr  (2015-04-29)
Created
Rothfels, K  (2015-02-12)
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