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

J Cell Biol. 2000 May 29;149(5):1107-16. doi: 10.1083/jcb.149.5.1107.

Abstract

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), 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.

MeSH terms

  • Actins / analysis
  • Actins / metabolism
  • Base Sequence
  • Biocompatible Materials
  • Blotting, Northern
  • Blotting, Western
  • Cells, Cultured
  • Collagen
  • Cytoskeleton / metabolism*
  • Drug Combinations
  • Endothelium, Vascular / chemistry
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / enzymology*
  • Extracellular Matrix / metabolism
  • GTP Phosphohydrolases / analysis
  • GTP Phosphohydrolases / genetics*
  • GTP Phosphohydrolases / metabolism*
  • Gene Expression Regulation, Enzymologic / physiology
  • Growth Substances / pharmacology
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism
  • Laminin
  • Molecular Sequence Data
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism
  • Neovascularization, Physiologic / physiology
  • Proteoglycans
  • RNA, Messenger / analysis
  • Sequence Homology, Amino Acid
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Transfection
  • Umbilical Arteries / cytology
  • Vinculin / analysis
  • Vinculin / metabolism
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Actins
  • Biocompatible Materials
  • Drug Combinations
  • Growth Substances
  • Immediate-Early Proteins
  • Laminin
  • Proteoglycans
  • RNA, Messenger
  • RRAD protein, human
  • Rrad protein, mouse
  • matrigel
  • Vinculin
  • Collagen
  • GTP Phosphohydrolases
  • Ges GTPase
  • GEM protein, human
  • Monomeric GTP-Binding Proteins
  • ras Proteins