P21RAS - AN ONCOPROTEIN FUNCTIONING IN GROWTH FACTOR-INDUCED SIGNAL-TRANSDUCTION

p21ras is a small GTPase that functions as a molecular switch in intracellular signal transduction pathways activated by a large variety of growth factors. In 50% of colorectal tumours, one of the genes for p21ras is mutated resulting in a constitutive active protein. Recently, progress has been made in the elucidation of the signalling pathways in which p21ras is involved. After a ligand binds to growth factor receptors, in particular receptor tyrosine kinases, a guanine nucleotide exchange factor is activated, which results in p21ras in the GTP-bound form. This GTP-bound form of p21ras interacts with the protein kinase raf1 and induces the activation of a kinase cascade, resulting in various cellular responses. This kinase cascade is part of an integrated network of both positive and negative signalling events.