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Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases.

http://www.ncbi.nlm.nih.gov/pubmed/9857026

The Rho-related small GTPases are critical elements involved in regulation of signal transduction cascades from extracellular stimuli to cell nucleus and cytoskeleton. The Dbl-like guanine nucleotide exchange factors (GEF) have been implicated in direct activation of these GTPases. Here we have identified a new member of the Dbl family, GEF-H1, by screening a human HeLa cell cDNA library. GEF-H1 encodes a 100-kDa protein containing the conserved structural array of a Dbl homology domain in tandem with a pleckstrin homology domain and is most closely related to the lfc oncogene, but additionally it contains a unique coiled-coil domain at the carboxyl terminus. Biochemical analysis reveals that GEF-H1 is capable of stimulating guanine nucleotide exchange of Rac and Rho but is inactive toward Cdc42, TC10, or Ras. Moreover, GEF-H1 binds to Rac and Rho proteins in both the GDP- and guanosine 5'-3-O-(thio)triphosphate-bound states without detectable affinity for Cdc42 or Ras. Immunofluorescence reveals that GEF-H1 colocalizes with microtubules through the carboxyl-terminal coiled-coil domain. Overexpression of GEF-H1 in COS-7 cells results in induction of membrane ruffles. These results suggest that GEF-H1 may have a direct role in activation of Rac and/or Rho and in bringing the activated GTPase to specific target sites such as microtubules.

Pubmed ID: 9857026 RIS Download

Mesh terms: 3T3 Cells | Amino Acid Sequence | Animals | COS Cells | Enzyme Activation | Fluorescent Antibody Technique | GTP Phosphohydrolases | GTP-Binding Proteins | GTPase-Activating Proteins | Gene Library | Guanine Nucleotide Exchange Factors | Guanine Nucleotides | Humans | Mice | Microtubule-Associated Proteins | Molecular Sequence Data | Open Reading Frames | Proteins | Proto-Oncogene Proteins | Recombinant Proteins | Rho Guanine Nucleotide Exchange Factors | Sequence Homology, Amino Acid | rac GTP-Binding Proteins | ras GTPase-Activating Proteins | ras Guanine Nucleotide Exchange Factors | rho GTP-Binding Proteins

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Associated grants

  • Agency: NIGMS NIH HHS, Id: GM53943

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