MAPK Family

The mitogen activated protein kinase (MAPK) family is conserved in evolution and is involved in diverse cellular processes including cell growth, proliferation, differentiation, survival, innate immunity and development. MAPKs transmit signals in the form of sequential phosphorylation events. The phospho-relay system is composed of three kinases: a MAPK kinase kinase (MAPKKK), a MAPK kinase (MAPKK) and a MAPK. Phosphorylation of the MAPKs occurs on a conserved dual-phosphorylation domain (Thr-Xxx-Tyr) leads to activation of the protein and the subsequent formation of dimers which translocate into the nucleus to activate downstream targets. Three major subfamilies of MAPK proteins have been defined: extracellular signal regulated kinases (ERK), the c-Jun amino-terminal kinases (JNK), and the p38 MAP kinases. The middle amino-acid residue of the conserved Thr-Xxx-Tyr dual-phosphorylation domain designates a MAPK protein to one of these subfamilies. In general, the ERK subfamily (TEY) is mainly activated by growth factors, p38 (TGY) by stress factors and JNK (TPY) are activated by stress-, differentiation- and growth-factors. It should be stressed here that scaffold proteins play an important role in the spatial–temporal organization of signaling complexes leading to activation of a specific cascade.