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© The Rockefeller University Press, 0021-9525/2000//1107 $5.00
The Journal of Cell Biology, Volume 149, Number 5, , 2000 1107-1116

Original Article

Ges, a Human Gtpase of the Rad/Gem/Kir Family, Promotes Endothelial Cell Sprouting and Cytoskeleton Reorganization



Julie Y. Pana, William E. Fielesa, Anne M. Whiteb, Mark M. Egertonb, and David S. Silbersteina

a Enabling Science and Technology-Biology, AstraZeneca Pharmaceuticals, Wilmington, Delaware 19850-5437
b Department of Cancer and Infection, AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, SK10 4TG United Kingdom
Enabling Science and Technology-Biology, AstraZeneca Pharmaceuticals, Wilmington, DE 19850-5437.(302) 886-1455(302) 886-4318

david.silberstein{at}astrazeneca.com

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. Goga, 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. Yewdell, 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 regulating endothelial cell sprouting), a human RGK protein expressed in the endothelium, functions as a potent morphogenic switch in endothelial cells (ECs). Ges function is sufficient to substitute for angiogenic growth factor/extracellular matrix (ECM) signals in promoting EC sprouting, since overexpression of Ges in ECs cultured on glass leads to the development of long cytoplasmic extensions and reorganization of the actin cytoskeleton. Ges function is also necessary for Matrigel-induced EC sprouting, since this event is blocked by its dominant negative mutant, GesT94N, predicted to prevent the activation of endogenous Ges through sequestration of its guanine nucleotide exchange factor. Thus, Ges appears to be a key transducer linking extracellular signals to cytoskeleton/morphology changes in ECs.

Key Words: angiogenesis • actin • morphology change • Matrigel

© 2000 The Rockefeller University Press

Mark M. Egerton's current address is Incyte Pharmaceuticals, 3174 Porter Drive, Palo Alto, CA 94304.

Abbreviations used in this paper: EC, endothelial cell; ECM, extracellular matrix; EST, expressed sequence tag; G domain, GTP-binding domain; GEF, guanine nucleotide exchange factor; Ges, GTPase regulating endothelial cell sprouting; GFP, green fluorescence protein; HPRT, hypoxanthine guanine phosphoribosyl transferase; HUAEC, human umbilical cord artery endothelial cell; ISH, in situ hybridization; RGK, Rad, Gem/Kir, and mRem; RT, reverse transcription.


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