Rho GTPases

The above mentioned Rho GTPases are glucosylated by the family of clostridial glucosylating cytotoxins. 

A subfamily of Rho proteins, the Rnd family of small GTPases, are always GTP-bound and seem to be regulated by expression and localization rather than by nucleotide exchange and hydrolysis. Many Rho GTPase effectors have been identified, including protein and lipid kinases, phospholipase D and numerous adaptor proteins. One of the best characterized effector of RhoA is Rho kinase, which phosphorylates and inactivates myosin phosphatase thereby RhoA causes activation of actomyosin complexes. Rho proteins are preferred targets of bacterial protein toxins ( bacterial toxins). 

Etienne-Manneville S, Hall A (2002) Rho GTPases in cell biology. Nature 420 629-635... 

Raftopoulou M, Hall A. Cell migration Rho GTPases lead the way. Dev Biol... 

Bishop AL. Rho GTPases and their effector proteins. Biochem J 2000 348 241-255. 

Clostridium difficile Targets a Rho GTPase General inhibitor of 79... 

Toxin B targets a Rho GTPase that is involved in the regulation of the actin cytoskeleton (79). 

Glucosyltransferases TcdA Clostridium diffioile AB Rho-GTPases Rho-signaling disturbed Pseudomembranous colitis... 

Prenylation has been implicated in the prevention of HIV infection. Statins have been used to inhibit HIV infection by interacting with Rho GTPases and suppress the intercellular adhesion required for viral entry. In another study with statins and HIV the mechanism of action was elucidated. The lypophilic statins... 

Aspenstrom, P. (1999) Effectors of the Rho GTPases. Current Opinion in Cell Biology 11, 95-102. 

Suzuki, N., Nakamura, S., Mano, H., and Kozasa, T. (2003). Gal2 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF. Proc. Natl. Acad. Sri. USA 100, 733-738. 

Subsequent studies have identified Rndl (Oinuma et al, 2003), another member of the Rho GTPase subfamily, and the ErbB-2 tyrosine kinase (Swiercz et al, 2004) in the regulation of RhoA by plexins. Additionally, an apparent requirement for interaction of plexin B with RhoGEFs for potentiation of angiogenesis by semaphorins (Basile et al., 2004) and activation of MAPK pathways (Aurandt et al, 2006) by plexin Bl was identified. Yet, direct evidence for the mechanism by which plexins achieve this activation of RhoA has been elusive. A simple mechanism would be localization of the RhoGEF to membranes on stimulation of the pathway as discussed in Section III.B. Evidence for this comes from a study (Oinuma et al, 2003) with Rndl, which can bind directly to plexin Bl. 

Barrett, K., Leptin, M., and Settleman, J. (1997). The Rho GTPase and a putative RhoGEF mediate a signaling pathway for the cell shape changes in Drosophila gastrulation. Cell 91, 905—915. 

Dutt, P., Nguyen, N., and Toksoz, D. (2004). Role of Lbc RhoGEF in G alphal2/ 13-induced signals to Rho GTPase. Cell. Signal. 16, 201-209. 

Longenecker, K. L., Lewis, M. E., Chikumi, H., Gutkind, J. S., and Derewenda, Z. S. (2001). Structure of the RGS-like domain from PDZ-RhoGEF Linking heterotri-meric g protein-coupled signaling to Rho GTPases. Structure 9, 559-569. 

---