GrinchGEF--a novel Rho-specific guanine nucleotide exchange factor.
RhoGTPases, which are activated by specific guanine nucleotide exchange factors (GEFs), play pivotal roles in several cellular functions. We identified a new RhoGEF (GrinchGEF) containing the typical Dbl homology domain, a putative WD40-like domain, and two predicted transmembrane helices. In contrast to most other RhoGEFs, it exhibits no sequence similarities to known pleckstrin homology domains. GrinchGEF mRNA was highly abundant in skeletal muscle and pancreas. Despite the predicted transmembrane domains, subcellular localization studies revealed a cytosolic distribution. In vitro, GrinchGEF induced the GDP/GTP exchange at RhoA, but not at Rac1 or Cdc42. In intact cells, GrinchGEF induced specifically Rho activation and enhanced RhoA-C-specific downstream effects.
Winkler
Stefan
S
Institut für Pharmakologie und Toxikologie, Fakultät für Klinische Medizin Mannheim, Universität Heidelberg, D-68169 Mannheim, Germany.
Mohl
Marion
M
Wieland
Thomas
T
Lutz
Susanne
S
D000595:Amino Acid Sequence; D000818:Animals; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009928:Organ Specificity; D064067:Rho Guanine Nucleotide Exchange Factors; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D020741:rho GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*
C577233:ARHGEF10L protein, human; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D020741:rho GTP-Binding Proteins