Fiche publication
Date publication
octobre 2020
Journal
Structure (London, England : 1993)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GOGL Gergo
Tous les auteurs :
Sok P, Gógl G, Kumar GS, Alexa A, Singh N, Kirsch K, Sebő A, Drahos L, Gáspári Z, Peti W, Reményi A
Lien Pubmed
Résumé
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.
Mots clés
ERK2, MAP kinase, MK2, NMR, RSK1, SAXS, X-ray crystallography, cellular signaling, p38, protein kinase complex
Référence
Structure. 2020 10 6;28(10):1101-1113.e5
