The RAC GTPase Cycle

RAC, a member of the family of RHO-like GTPases, cycles between a GDP- and a GTP-bound state. When GTP-bound, it interacts with various effector molecules that elicit downstream responses including notably actin cytoskeletal reorganisation. Multiple mechanisms control RAC activity including control of nucleotide binding and hydrolysis by GEFs (Guanine Nucleotide Exchange Factors) and GTPase Activating Proteins (GAPs) respectively, regulation of subcellular localisation, modulation of RAC protein levels, and post-translational modification including isoprenylation and as we and others have demonstrated ubiquitylation and SUMOylation (Castillo-Lluva et al. Oncogene 2013; Castillo-Lluva et al. Nat Cell Biol. 2010).

The RAC GTPase Cycle.
RAC cycles between an inactive, GDP-bound form, and an active GTP-bound form. Signals from outside the cell, mediated by transmembrane receptors [for example G-protein coupled receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs)], converge on the Guanine Nucleotide Exchange Factors (GEFS), which drive RAC into its active state. Once activated, RAC can bind to a wide range of effectors, which in turn influence both normal and oncogenic cell processes. Other mechanisms, such as stabilisation of the active form of RAC by Sumoylation, or sequestration of the inactive form by Guanine Nucleotide Dissociation factors (GDIs) can also influence the level of RAC signalling.