The MAP-Kinase (MAPK) signalling pathway

The MAPK pathway is dysregulated in more than 50 % of all human tumors. The pathway starts with the activation of a receptor tyrosine kinase, which transmits the signal to a protein that catalyzes the exchange of the guanine nucleotide GDP for GTP associated with the membrane bound protein Ras. The activated GTP-bound form of Ras activates the kinase B-Raf, which itself phosphorylates several cytosolic proteins and thus transmits the signal into the cell. The RAS gene carries point mutations in a high number of human cancers. The mutated Ras protein cannot be inactivated by the GTPase activating protein and is constitutively active, even in the absence of an upstream signal. Therapeutic approaches to inhibit MAPK signaling are based on molecules, which inhibit the EGF receptor, the Ras protein or the Raf kinase.