Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member.
Several guanine nucleotide exchange factors (GEFs) for Rho-GTPases have been identified, all of them containing a Dbl homology (DH) and pleckstrin homology (PH) domain, but exhibiting different specificities to the Rho family members, Rho, Rac and Cdc42. We report here that KIAA0380, a protein with a tandem DH/PH domain, an amino-terminal PDZ domain and a regulator of G protein signalling (RGS) homology domain, is a specific GEF for RhoA, but not for Rac1 and Cdc42, as determined by GDP release, guanosine 5'-O-(3-thio)triphosphate (GTPgammaS) binding and protein binding assays. When expressed in J82 cells, DH/PH domain-containing forms of KIAA0380 induced actin stress fibers, whereas expression of the RGS homology domain prevented lysophosphatidic acid (LPA)-induced stress fiber formation.
Rümenapp
U
U
Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstr. 55, D-45122, Essen, Germany. ulrich.ruemenapp@uni-essen.de
Blomquist
A
A
Schwörer
G
G
Schablowski
H
H
Psoma
A
A
Jakobs
K H
KH
D000199:Actins / Q000378:metabolism; D002384:Catalysis; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000145:classification; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D064067:Rho Guanine Nucleotide Exchange Factors; D014407:Tumor Cells, Cultured; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
C577234:ARHGEF11 protein, human; D000199:Actins; D020662:Guanine Nucleotide Exchange Factors; D006150:Guanine Nucleotides; C057811:MCF2 protein, human; D009842:Oligopeptides; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D064067:Rho Guanine Nucleotide Exchange Factors; C047981:arginyl-glycyl-aspartic acid; D020742:rhoA GTP-Binding Protein