Reactome | p-S MAPK6,4 binds MAPKAPK5

p-S MAPK6,4 binds MAPKAPK5

Stable Identifier

R-HSA-5687091

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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In proliferating cells, p-S189 MAPK6 and pS-186 MAPK4 bind to the MAPK effector kinase MAPKAPK5 (also known as MK5) through an FRIEDE motif in the C-terminal region (Perander et al, 2008; Deleris et al, 2008; Aberg et al, 2009). This motif, which is unique to MAPK6 and MAPK4 binds to the C-terminal 50 residues of MAPKAKP5 and is required for both the cytoplasmic accumulation and the activation of MAPKAPK5 (Aberg et al, 2009; Aberg et al, 2006; Seternes et al, 2004; Deleris et al, 2008). Cytoplasmic redistribution of MAPKAPK5 depends on the protein-protein interaction with MAPK6 or 4 and not the activity of any of the kinases, as cytoplasmic localization is abrogated by disruption of the interaction interface but not by kinase-dead versions of MAPK6, 4 or MAPKAPK5 itself (Aberg et al, 2006; Seternes et al, 2004).

Literature References

PubMed ID	Title	Journal	Year
16971392	Regulation of MAPK-activated protein kinase 5 activity and subcellular localization by the atypical MAPK ERK4/MAPK4 Aberg, E, Perander, M, Johansen, B, Julien, C, Meloche, S, Keyse, SM, 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, Coulombe, P, Rodier, G, Tanguay, PL, Meloche, S	J. Cell. Physiol.	2008
19473979	Docking of PRAK/MK5 to the atypical MAPKs ERK3 and ERK4 defines a novel MAPK interaction motif Aberg, E, Torgersen, KM, Johansen, B, Keyse, SM, Perander, M, Seternes, OM	J. Biol. Chem.	2009
15577943	Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway Seternes, OM, Mikalsen, T, Johansen, B, Michaelsen, E, Armstrong, CG, Morrice, NA, Turgeon, B, Meloche, S, Moens, U, Keyse, SM	EMBO J.	2004
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