PAK1,2,3 phosphorylates MAPK6,4

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R-HSA-5687086
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Reaction
Species
Homo sapiens
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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
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
17161475 Atypical mitogen-activated protein kinases: structure, regulation and functions

Coulombe, P, Meloche, S

Biochim. Biophys. Acta 2007
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
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Title
protein serine/threonine kinase activity of p-S,T-PAK1,2,3 [cytosol]
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