Map kinases

MAP kinases (MAP stands for"mitogen-activated protein") belong to the class of protein kinases and here again to the serine/threonine kinases.

MAP kinases are important key enzymes of cell metabolism and phosphorylate proteins at serine or threonine residues. MAP kinases are part of highly conserved signaling cascades that control the induction and regulation of various phases of the cell cycle, including cell growth, differentiation, apoptosis, and migration.

Chemically, MAP kinases are protein kinases (molar mass 36-44 kDa) that phosphorylate other proteins at specific serine/threonine residues (serine-threonine kinases).

MAP kinases (MAP-K) are directly activated by phosphorylation at two sites: a tyrosine residue and a threonine residue. Phosphorylation occurs through MAP-KK(MAP kinase kinase; see MAP kinase signaling pathway below).

Activated MAP kinases accumulate in the nucleus and phosphorylate nuclear transcription factors. This regulates a large number of target genes and thus numerous key cellular functions. As soon as the MAP kinases are dephosphorylated and thus inactivated, they redistribute in the cytosol and are available for further activation cycles.

The high mutation rate in the MAP kinase signalling pathway highlights its key role in melanoma genesis. A growth factor that is often pathologically activated by mutation or amplification in this signaling pathway is the KIT receptor, which is mainly altered in acute (36%) and mucosal (39%) melanomas and in melanomas of chronically light-exposed skin.

Orally available multi-kinase inhibitors (e.g. sorafenib) now play an important role in oncology.