p-S MAPK6,4 phosphorylate MAPKAPK5

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Activated MAPK6 and MAPK4 promote the phosphorylation of MAPKAPK5 on threonine 182, activating it (Deleris et al, 2008; Aberg et al, 2006; Aberg et al, 2009; Seternes et al, 2004; Perander et al, 2008). Thr182 phosphorylation may result in part from autophosphorylation stimulated by MAPK6 binding, rather than direct phosphorylation by MAPK6, as an ATP-binding pocket mutant of MAPKAKP5 is not phosphorylated in response to MAPK6 (Seternes et al, 2004; Schumacher et al, 2004). There is conflicting evidence as to whether a catalytically inactive MAPK6 mutant can promote MAPKAPK5 phosphorylation (Schumacher et al, 2004; Seternes et al, 2004; Deleris et al, 2008). These conflicting results can be reconciled by the suggestion that inactive MAPK6 promotes MAPKAPK5 phosphorylation through heterodimerization with active MAPK4 (Kant et al, 2006). Phosphorylation of MAPKAPK5 in response to MAPK4/6 signaling promotes its cytoplasmic relocalization (Shumacher et al, 2004; Aberg et al, 2006; Deleris et al, 2008; Seternes et al, 2004).

Literature References
PubMed ID Title Journal Year
16973613 Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5

Kispert, A, Schumacher, S, Kant, S, Kotlyarov, A, Singh, MK, Gaestel, M

J. Biol. Chem. 2006
16971392 Regulation of MAPK-activated protein kinase 5 activity and subcellular localization by the atypical MAPK ERK4/MAPK4

Meloche, S, Julien, C, Johansen, B, Aberg, E, Keyse, SM, Perander, M, Seternes, OM

J. Biol. Chem. 2006
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, Meloche, S, Rodier, G, Coulombe, P, Tanguay, PL

J. Cell. Physiol. 2008
15538386 Scaffolding by ERK3 regulates MK5 in development

Schumacher, S, Visel, A, Kant, S, Kotlyarov, A, Shi, Y, Gruber, AD, Gaestel, M, Laass, K

EMBO J. 2004
19473979 Docking of PRAK/MK5 to the atypical MAPKs ERK3 and ERK4 defines a novel MAPK interaction motif

Johansen, B, Aberg, E, Torgersen, KM, Perander, M, Keyse, SM, Seternes, OM

J. Biol. Chem. 2009
15577943 Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway

Meloche, S, Johansen, B, Morrice, NA, Mikalsen, T, Moens, U, Armstrong, CG, Keyse, SM, Turgeon, B, Michaelsen, E, Seternes, OM

EMBO J. 2004
18248330 The Ser(186) phospho-acceptor site within ERK4 is essential for its ability to interact with and activate PRAK/MK5

Johansen, B, Aberg, E, Keyse, SM, Perander, M, Dreyer, B, Guldvik, IJ, Seternes, OM, Outzen, H

Biochem. J. 2008
Catalyst Activity

protein serine/threonine kinase activity of p-S MAPK6,4:MAKPAPK5 [nucleoplasm]

Orthologous Events
Cite Us!