---

   In their GDP-bound forms, members of the Rho family exist in cytosol in complex with an inhibitory protein, RhoGDI. This complex requires and is presumed to be mediated by protein iosprenylation. RhoGDI seems to block the availability of the isoprenyl group, preventing association with the membrane. Most of the targets of Rho's are in the membrane, and Rho proteins translocate to the membrane upon activation. As part of the activation mechanism, Rho becomes "loaded" with GTP to produce an active conformation. This loading involves the participation of one or more exchange factors, and inactivation involved hydrolysis of GTP back to GDP. The upstream regulation of Rac is poorly understood, but may involve PI 3-kinase based upon inhibition studies using the PI 3-kinase inhibitor wortmannin. Candidate exchange factors include Dbl, TIAM-1, BCR, ABR and many others.

Review:

Olson, M.F. (1996) "Guanine Nucleotide Exchange Factors for the Rho GTPases: A Role in Human Diseases?" J. Mol. Med. 74, 563-571.

Nisimoto, Y., Freeman, J.F.R., Motalebi, S.A., Hirshberg, M. and Lambeth, J.D. (1997) "Rac binding to p67phox: Structural Basis for Ineractions of the Rac1 Effector Region and Insert Region with Components of the Respiratory Burst Oxidase" J. Biol. Chem. 271, in press.