Rho-family GTPases: it's not only Rac and Rho (and I like it)

Abstract

The Rho-family proteins make up a major branch of the Ras superfamily of small GTPases. To date, 22 human genes encoding at least 25 proteins have been described. The best known 'classical' members are RhoA, Rac1 and Cdc42. Highly related isoforms of these three proteins have not been studied as intensively, in part because it has been assumed that they are functionally identical to their better-studied counterparts. This now appears not to be the case. Variations in C-terminal-signaled modifications and subcellular targeting cause otherwise highly biochemically related isoforms (e.g. RhoA, RhoB and RhoC) to exhibit surprisingly divergent biological activities. Whereas the classical Rho GTPases are regulated by GDP/GTP cycling, other Rho GTPases are also regulated by other mechanisms, particularly by transcriptional regulation. Newer members of the family possess additional sequence elements beyond the GTPase domain, which suggests they exhibit yet other mechanisms of regulation.