Ras in epidermal proliferation

The Ras family of small GTPases (H-Ras, N-Ras and K-Ras) constitutes a central node in the transmission of mitogenic signals from cell surface receptors to the cell cycle machinery. In general, activation of membrane receptors causes GTP loading of Ras proteins via guanosine nucleotide exchange factor (GEF) stimulation. Loading of GTP promotes conformational changes that ultimately allow binding and subsequent activation of a battery of effector molecules, such as the Raf kinases, the catalytic subunits of phosphatidylinositol 3-kinase (PI3K) or the Ral-GEF family of proteins. Ras-mediated signaling is terminated upon GTP hydrolysis, a reaction that leads to an inactive conformation characterized by a GDP-bound state. This hydrolysis is catalyzed by the intrinsic GTPase activity of Ras proteins, a rather slow reaction that can be accelerated by a familiy of GTPase-activating proteins (GAPs) [1].