Reactome | Activated MAPKs phosphorylate MAP2K1

Activated MAPKs phosphorylate MAP2K1

Stable Identifier

R-HSA-5674496

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

Locations in the PathwayBrowser

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Signal Transduction (Homo sapiens)

- MAPK family signaling cascades (Homo sapiens)
  - MAPK1/MAPK3 signaling (Homo sapiens)
    - RAF/MAP kinase cascade (Homo sapiens)
      - Negative regulation of MAPK pathway (Homo sapiens)
        
        Negative feedback regulation of MAPK pathway (Homo sapiens)
        
        Activated MAPKs phosphorylate MAP2K1 (Homo sapiens)

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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 Catalanotti, F, Reyes, G, Jesenberger, V, Galabova-Kovacs, G, de Matos Simoes, R, Carugo, O, Baccarini, M	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 Xu, BE, Wilsbacher, JL, Collisson, T, Cobb, MH	J. Biol. Chem.	1999
8013650	Growth factor-stimulated MAP kinase induces rapid retrophosphorylation and inhibition of MAP kinase kinase (MEK1) Brunet, A, Pages, G, Pouyssegur, J	FEBS Lett	1994