p-S MAPK6,4 binds MAPKAPK5

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).

在细胞增殖过程中，磷酸化p-S189 MAPK6和pS-186 MAPK4通过C端区域中的FRIEDE基序与MAPK效应激酶MAPKAPK5（亦称MK5）相结合（Perander等，2008；Deleris等，2008；Aberg等，2009）。此基序，为MAPK6和MAPK4所特有，能够与MAPKAPK5的C端50个氨基酸残基结合，并对于MAPKAPK5在细胞质中的积累及其激活至关重要（Aberg等，2009；Aberg等，2006；Seternes等，2004；Deleris等，2008）。MAPKAPK5在细胞质中的重分布依赖于与MAPK6或4的蛋白-蛋白相互作用，而非任何激酶的活性，因为破坏相互作用界面将导致细胞质定位的丧失，而MAPK6、4或MAPKAPK5本身的激酶失活版本则不会影响这一过程（Aberg等，2006；Seternes等，2004）。