ABSTRACT

MARTIN AUGSTEN, ANIKA BÖTTCHER, RAINER SPANBROEK, IGNACIO RUBIO, AND KARLHEINZ FRIEDRICH

2.1 BACKGROUND

The prototypical Ras isoforms H-Ras, K-Ras and N-Ras (collectively Ras) are membrane-associated small G-proteins that cycle between an active, GTP-bound and an inactive, GDP-bound state. Ras becomes activated, that is GTP-loaded, by guanine nucleotide exchange factors (GEFs) such as Sos or RasGRP, which are themselves engaged and activated downstream of various cell surface receptors via adapter proteins, like Shc and Grb-2 and/or via second messenger lipids like phosphatidic acid or diacylglycerol [1,2]. Inactivation of GTP-loaded Ras occurs through a GTP-hydrolase (GTPase) activity intrinsic to Ras and enhancement of this reaction by GTPase activating proteins (GAPs) [1,3]. Ras function is also controlled

by a series of obligatory post-translational modifications which include an initial farnesylation step and the reversible attachment of palmitate groups to N-Ras and H-Ras [4]. Although many details of this complex processing remain unknown, it is well established that the correct posttranslational processing is required to direct Ras to cellular membranes and specific microdomains within the plasma membrane (PM) [5].