TAO (thousand and one amino acid) protein kinase 2 (TAO2) activates MAP/ERK kinases (MEKs) 3, 4, and 6 toward their substrates p38 MAP kinase JNK/SAPK. This and more recent work has led to the proposal that the TAO protein kinases play an essential role in signaling from physiological agonists to the stress-responsive p38 MAPKs. Autophosphorylation of TAO may play a role in the mechanism of TAO activation. The MEK binding domain of TAO is autophosphorylated on both serine and threonine residues and Ser181 is located within this domain.