ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Activated by threonine and tyrosine phosphorylation (By similarity). Activated by the MAP kinase kinase MKK2. Activated by the MAP kinase kinase MKK6 in vitro. The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. Autophosphorylated on threonine and tyrosine residues. Dually phosphorylated on Thr-201 and Tyr-203, which activates the enzyme. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.