MAP2K1 and cancer: Although all the disease-associated MEK1 mutants exhibited moderate kinase activity independent of MEK1 T-loop phosphorylation as confirmed by the higher kinase activities of their T-loop unphosphorylatable AA mutants versus WT MEK1, the cancer-, but not the RASopathy-, associated mutants can additionally autophosphorylate their own T-loops, thereby leading to strong and oncogenic kinase activities.