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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2000-5-17
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pubmed:databankReference |
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pubmed:abstractText |
Few molecular events important to platelet biogenesis have been identified. Mice homozygous for the spontaneous, recessive mutation gunmetal (gm) have prolonged bleeding, thrombocytopenia, and reduced platelet alpha- and delta-granule contents. Here we show by positional cloning that gm results from a G-->A substitution mutation in a splice acceptor site within the alpha-subunit of Rab geranylgeranyl transferase (Rabggta), an enzyme that attaches geranylgeranyl groups to Rab proteins. Most Rabggta mRNAs from gm tissues skipped exon 1 and lacked a start codon. Rabggta protein and Rab geranylgeranyl transferase (GGTase) activity were reduced 4-fold in gm platelets. Geranylgeranylation and membrane association of Rab27, a Rab GGTase substrate, were significantly decreased in gm platelets. These findings indicate that geranylgeranylation of Rab GTPases is critical for hemostasis. Rab GGTase inhibition may represent a new treatment for thrombocytosis and clotting disorders.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-10601342,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-1321151,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-1427786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-1525821,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-1850747,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-1912584,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-3877532,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-508939,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-7592656,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-7703484,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-7733457,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-8294464,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-8298418,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-8380507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-8490171,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-8505342,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-8621375,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-8833241,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-9066979,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-9154319,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-9175730,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-9261061,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-9585243,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-9607139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-9677305,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-9705524,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10737774-9712825
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0027-8424
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pubmed:author |
pubmed-author:DetterJ CJC,
pubmed-author:KingsmoreS FSF,
pubmed-author:LUCC,
pubmed-author:McMurtrieE BEB,
pubmed-author:MishraV SVS,
pubmed-author:MulesE HEH,
pubmed-author:NovakE KEK,
pubmed-author:SeabraM CMC,
pubmed-author:SwankR TRT,
pubmed-author:TchernevV TVT,
pubmed-author:WallaceM RMR,
pubmed-author:ZhangQQ
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4144-9
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10737774-Alkyl and Aryl Transferases,
pubmed-meshheading:10737774-Animals,
pubmed-meshheading:10737774-Blood Platelets,
pubmed-meshheading:10737774-Cell Division,
pubmed-meshheading:10737774-Chromosomes, Artificial, Yeast,
pubmed-meshheading:10737774-Genotype,
pubmed-meshheading:10737774-Mice,
pubmed-meshheading:10737774-Mice, Inbred C57BL,
pubmed-meshheading:10737774-Mice, Mutant Strains,
pubmed-meshheading:10737774-Molecular Sequence Data,
pubmed-meshheading:10737774-Mutation,
pubmed-meshheading:10737774-Phenotype,
pubmed-meshheading:10737774-Protein Prenylation,
pubmed-meshheading:10737774-rab GTP-Binding Proteins
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pubmed:year |
2000
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pubmed:articleTitle |
Rab geranylgeranyl transferase alpha mutation in the gunmetal mouse reduces Rab prenylation and platelet synthesis.
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pubmed:affiliation |
Departments of Medicine, Molecular Genetics and Microbiology, Pathology and Laboratory Medicine, and Pediatrics, and Center for Mammalian Genetics, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA.
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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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