Module 5: Figure dual-specificity MKP
Mode of action of dual-specificity mitogen-activated protein kinase (MAPK) phosphatase.
Extracellular-signal-regulated kinase 2 (RK2), which is one of the main components of mitogen-activated protein kinase (MAPK) signalling, is phosphorylated on threonine (T) and tyrosine (Y) by MEK1/2, a dual-specificity MAPK kinase (Module 2: Figure ERK signalling). These phosphorylation events are reversed by MAPK phosphatase-3 (MKP-3). The specificity of the interaction between ERK2 and MKP-3 depends upon the latter having a kinase interaction motif (KIM) that binds to a specific site on ERK. This interaction enables the protein tyrosine phosphatase (PTP) domain to dephosphorylate the two phosphorylated residues on ERK2, thus curtailing its ability to stimulate downstream responses.