Ges, a human GTPase of the Rad/Gem/Kir family, promotes endothelial cell sprouting and cytoskeleton reorganization

Rad, Gem/Kir, and mRem (RGK) represent a unique GTPase family with largely unknown functions (Reynet, C., and C.R, Kahn. 1993. Science. 262: 1441-1444 ; Cohen. L,, R. Mohr, Y. Chen, M. Huang, R. Kato. D, Dorin, F.Tamanoi, A. G oga, D, Afar, N, Rosenberg, and O, Witte. Proc. Natl. Acad. Sci. USA. 1994, 91:12448-12452; Maguire, J.,T. Santoro, P. Jensen, U, Siebenlist. J. Yewde ll, and K, Kelly. 1994, Science. 265:241-244; Finlin, B,S., and D,A. Andres . 1997. J. Biol. Chem, 272:21982-21988). We report that Ges (GTPase regulat ing endothelial cell sprouting), a human RGK protein expressed in the endot helium, functions as a potent morphogenic switch in endothelial cells (ECs) . Ges function is sufficient to substitute for angiogenic growth factor/ext racellular matrix (ECM) signals in promoting EC sprouting, since overexpres sion of Ges in ECs cultured on glass leads to the development of long cytop lasmic extensions and reorganization of the actin cytoskeleton. Ges functio n is also necessary for Matrigel-induced EC sprouting, since this event is blocked by its dominant negative mutant, Ges(T94N), pre dieted to prevent t he activation of endogenous Ges through sequestration of its guanine nucleo tide exchange factor. Thus, Ges appears to be a key transducer linking extr acellular signals to cytoskeleton/morphology changes in ECs.