MAP Kinase-Mediated Activation of RSK1 and MK2 Substrate Kinases.
Mitogen-activated protein kinases (MAPKs) control essential eukaryotic signaling pathways. While much has been learned about MAPK activation, much less is known about substrate recruitment and specificity. MAPK substrates may be other kinases that are crucial to promote a further diversification of the signaling outcomes. Here, we used a variety of molecular and cellular tools to investigate the recruitment of two substrate kinases, RSK1 and MK2, to three MAPKs (ERK2, p38α, and ERK5). Unexpectedly, we identified that kinase heterodimers form structurally and functionally distinct complexes depending on the activation state of the MAPK. These may be incompatible with downstream signaling, but naturally they may also form structures that are compatible with the phosphorylation of the downstream kinase at the activation loop, or alternatively at other allosteric sites. Furthermore, we show that small-molecule inhibitors may affect the quaternary arrangement of kinase heterodimers and thus influence downstream signaling in a specific manner.
['Sok|Péter|P|', 'Gógl|Gergő|G|', 'Kumar|Ganesan Senthil|GS|', 'Alexa|Anita|A|', 'Singh|Neha|N|', 'Kirsch|Klára|K|', 'Sebő|Anna|A|', 'Drahos|László|L|', 'Gáspári|Zoltán|Z|', 'Peti|Wolfgang|W|', 'Reményi|Attila|A|']
D001665:Binding Sites D018360:Crystallography, X-Ray D004789:Enzyme Activation D057809:HEK293 Cells D006801:Humans D047908:Intracellular Signaling Peptides and Proteins D009682:Magnetic Resonance Spectroscopy D019950:Mitogen-Activated Protein Kinase 1 D048308:Mitogen-Activated Protein Kinase 14 D048054:Mitogen-Activated Protein Kinase 7 D046912:Multiprotein Complexes D010766:Phosphorylation D047428:Protein Kinase Inhibitors D055503:Protein Multimerization D017346:Protein Serine-Threonine Kinases D020836:Protein Structure, Quaternary D038744:Ribosomal Protein S6 Kinases, 90-kDa D053838:Scattering, Small Angle D014961:X-Ray Diffraction
RSK1 MK2 ERK2 MAP kinase NMR SAXS X-ray crystallography cellular signaling p38 protein kinase complex