biostudies-literatureUnknown301(9)Juyoux PKinases are a diverse group of enzymes that use ATP to phosphorylate a variety of substrates. Protein kinases evolved in eukaryotes as important mediators of cell signaling that target specific amino acid side chains to modulate downstream protein function. Among them, the mitogen-activated protein kinases (MAPKs) are a family of intracellular protein kinases that form signaling cascades responding to a number of stimuli, which control fundamental mechanisms such as proliferation, differentiation, inflammation, and cell death. Signals propagate through consecutive kinases which eventually phosphorylate and activate a MAPK. Here, we show that the dual-specificity threonine/tyrosine mitogen-activated protein kinase kinases (MAP2Ks or MEKs) are able to phosphorylate and activate their substraThe Journal of biological chemistry110578https://www.ebi.ac.uk/biostudies/studies/S-EPMC12446509biostudies-literatureDual-specificity mitogen-activated protein kinase kinases can use ADP to phosphorylate MAP kinases invitro.PMC12446509Bowler MWvon Velsen JJuyoux PPellegrini EfalseDual-specificity mitogen-activated protein kinase kinases can use ADP to phosphorylate MAP kinases invitro.Kinases are a diverse group of enzymes that use ATP to phosphorylate a variety of substrates. Protein kinases evolved in eukaryotes as important mediators of cell signaling that target specific amino acid side chains to modulate downstream protein function. Among them, the mitogen-activated protein kinases (MAPKs) are a family of intracellular protein kinases that form signaling cascades responding to a number of stimuli, which control fundamental mechanisms such as proliferation, differentiation, inflammation, and cell death. Signals propagate through consecutive kinases which eventually phosphorylate and activate a MAPK. Here, we show that the dual-specificity threonine/tyrosine mitogen-activated protein kinase kinases (MAP2Ks or MEKs) are able to phosphorylate and activate their substra2025-01-01T00:00:00Z2025 Aug2026-06-03T15:24:19.533Z2026-04-29T03:12:03.138ZS-EPMC124465094078444910.1016/j.jbc.2025.110578