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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
52
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pubmed:dateCreated |
1999-2-3
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pubmed:databankReference |
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arhgef2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/GTP Phosphohydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GTPase-Activating Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Guanine Nucleotide Exchange Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Guanine Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/rac GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ras GTPase-Activating Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ras Guanine Nucleotide Exchange...,
http://linkedlifedata.com/resource/pubmed/chemical/rho GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/rho GTPase-activating protein
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
34954-60
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9857026-3T3 Cells,
pubmed-meshheading:9857026-Amino Acid Sequence,
pubmed-meshheading:9857026-Animals,
pubmed-meshheading:9857026-COS Cells,
pubmed-meshheading:9857026-Enzyme Activation,
pubmed-meshheading:9857026-Fluorescent Antibody Technique,
pubmed-meshheading:9857026-GTP Phosphohydrolases,
pubmed-meshheading:9857026-GTP-Binding Proteins,
pubmed-meshheading:9857026-GTPase-Activating Proteins,
pubmed-meshheading:9857026-Gene Library,
pubmed-meshheading:9857026-Guanine Nucleotide Exchange Factors,
pubmed-meshheading:9857026-Guanine Nucleotides,
pubmed-meshheading:9857026-Humans,
pubmed-meshheading:9857026-Mice,
pubmed-meshheading:9857026-Microtubule-Associated Proteins,
pubmed-meshheading:9857026-Molecular Sequence Data,
pubmed-meshheading:9857026-Open Reading Frames,
pubmed-meshheading:9857026-Proteins,
pubmed-meshheading:9857026-Proto-Oncogene Proteins,
pubmed-meshheading:9857026-Recombinant Proteins,
pubmed-meshheading:9857026-Sequence Homology, Amino Acid,
pubmed-meshheading:9857026-rac GTP-Binding Proteins,
pubmed-meshheading:9857026-ras GTPase-Activating Proteins,
pubmed-meshheading:9857026-ras Guanine Nucleotide Exchange Factors,
pubmed-meshheading:9857026-rho GTP-Binding Proteins
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pubmed:year |
1998
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pubmed:articleTitle |
Cloning and characterization of GEF-H1, a microtubule-associated guanine nucleotide exchange factor for Rac and Rho GTPases.
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pubmed:affiliation |
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA. yren@bcm.tmc.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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