Reactome | PAK1,2,3 phosphorylates MAPK6,4

PAK1,2,3 phosphorylates MAPK6,4

Stable Identifier

R-HSA-5687086

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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The atypical MAPKs MAPK6 (also known as ERK3) and MAPK4 (also known as ERK4) lack the conserved activation loop T-X-Y motif of the conventional MAPKs, and are thus not substrates for the dual-specificity MAPK kinases (reviewed in Coulombe and Meloche, 2007; Cargnello and Roux, 2011). The corresponding loop of MAPK6 and 4 instead contain a S-E-G motif that is phosphorylated at serine 189 and serine 186, respectively, by class I p21 activated kinases (PAKs) in a RAC- or CDC42-dependent manner (Deleris et al, 2008; Perander et al, 2008; Deleris et al, 2011; De La Mota-Peynado et al, 2011). Phosphorylation of the atypical MAPKs is not responsive to any identified extracellular stimulus, but rather occurs constitutively (Deleris et al, 2008).

Literature References

PubMed ID	Title	Journal	Year
17161475	Atypical mitogen-activated protein kinases: structure, regulation and functions Coulombe, P, Meloche, S	Biochim. Biophys. Acta	2007
21317288	Identification of the atypical MAPK Erk3 as a novel substrate for p21-activated kinase (Pak) activity De la Mota-Peynado, A, Chernoff, J, Beeser, A	J. Biol. Chem.	2011
18720373	Activation loop phosphorylation of the atypical MAP kinases ERK3 and ERK4 is required for binding, activation and cytoplasmic relocalization of MK5 Déléris, P, Rousseau, J, Coulombe, P, Rodier, G, Tanguay, PL, Meloche, S	J. Cell. Physiol.	2008
18248330	The Ser(186) phospho-acceptor site within ERK4 is essential for its ability to interact with and activate PRAK/MK5 Perander, M, Aberg, E, Johansen, B, Dreyer, B, Guldvik, IJ, Outzen, H, Keyse, SM, Seternes, OM	Biochem. J.	2008
21177870	Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathway Déléris, P, Trost, M, Topisirovic, I, Tanguay, PL, Borden, KL, Thibault, P, Meloche, S	J. Biol. Chem.	2011
21372320	Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases Cargnello, M, Roux, PP	Microbiol. Mol. Biol. Rev.	2011