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

被引:38
作者
Pan, JY
Fieles, WE
White, AM
Egerton, MM
Silberstein, DS [1 ]
机构
[1] AstraZeneca Pharmaceut, Enabling Sci & Technol Biol, Wilmington, DE 19850 USA
[2] AstraZeneca Pharmaceut, Dept Canc & Infect, Macclesfield SK10 4TG, Cheshire, England
关键词
angiogenesis; actin; morphology change; Matrigel;
D O I
10.1083/jcb.149.5.1107
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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, Ges(T94N), pre dieted 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.
引用
收藏
页码:1107 / 1115
页数:9
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