Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a Db1 family member

Several guanine nucleotide exchange factors (GEFs) for Rho-GTPases have bee n identified, all of them containing a Dbl homology (DH) and pleckstrin hom ology (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 pr otein signalling (RGS) homology domain, is a specific GEF for RhoA, but not for Rad and Cdc42, as determined by GDP release, guanosine 5'-O-(3-thio)tr iphosphate (GTP gamma S) binding and protein binding assays. When expressed in J82 cells, DHIPH domain-containing forms of KIAA0380 induced actin stre ss fibers, whereas expression of the RGS homology domain prevented lysophos phatidic acid (LPA)-induced stress fiber formation. (C) 1999 Federation of European Biochemical Societies.