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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 |
2004-12-21
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pubmed:abstractText |
Vav family proteins are guanine nucleotide exchange factors for the Rho/Rac family of small GTP-binding proteins. In addition, they have domains that mediate protein-protein interactions, including one Src homology 2 (SH2) and two Src homology 3 (SH3) domains. Vav1, Vav2, and Vav3 play a crucial role in the regulation of phospholipase C gamma (PLC gamma) isoforms by immuno-tyrosine-based activation motif (ITAM)-coupled receptors, including the T- and B-cell antigen receptors. We have reported in platelets, however, that Vav1 and Vav2 are not required for activation of PLC gamma 2 in response to stimulation of the ITAM-coupled collagen receptor glycoprotein VI (GPVI). Here we report that Vav3 is tyrosinephosphorylated upon activation of GPVI but that Vav3-deficient platelets also exhibit a normal response upon activation of the ITAM receptor. In sharp contrast, platelets deficient in both Vav1 and Vav3 show a marked inhibition of aggregation and spreading upon activation of GPVI, which is associated with a reduction in tyrosine phosphorylation of PLC gamma 2. The phenotype of Vav1/2/3 triple-deficient platelets is similar to that of Vav1/3 double-deficient cells. These results demonstrate that Vav3 and Vav1 play crucial but redundant roles in the activation of PLC gamma 2 by GPVI. This is the first time that absolute redundancy between two protein isoforms has been observed with respect to the regulation of PLC gamma 2 in platelets.
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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/Agammaglobulinaemia tyrosine kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD36,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Guanine Nucleotide Exchange Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-vav,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Syk kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/VAV1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/VAV3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vav1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Vav2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Vav3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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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 |
24
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
53955-62
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:15456756-Animals,
pubmed-meshheading:15456756-Antigens, CD36,
pubmed-meshheading:15456756-Blood Platelets,
pubmed-meshheading:15456756-Cell Cycle Proteins,
pubmed-meshheading:15456756-Collagen,
pubmed-meshheading:15456756-Enzyme Activation,
pubmed-meshheading:15456756-Enzyme Precursors,
pubmed-meshheading:15456756-Guanine Nucleotide Exchange Factors,
pubmed-meshheading:15456756-Humans,
pubmed-meshheading:15456756-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15456756-Mice,
pubmed-meshheading:15456756-Mice, Knockout,
pubmed-meshheading:15456756-Oncogene Proteins,
pubmed-meshheading:15456756-Phospholipase C gamma,
pubmed-meshheading:15456756-Phosphorylation,
pubmed-meshheading:15456756-Phosphotyrosine,
pubmed-meshheading:15456756-Platelet Activation,
pubmed-meshheading:15456756-Protein-Tyrosine Kinases,
pubmed-meshheading:15456756-Proto-Oncogene Proteins,
pubmed-meshheading:15456756-Proto-Oncogene Proteins c-vav,
pubmed-meshheading:15456756-Receptors, Collagen,
pubmed-meshheading:15456756-Type C Phospholipases,
pubmed-meshheading:15456756-src-Family Kinases
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pubmed:year |
2004
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pubmed:articleTitle |
Vav1 and vav3 have critical but redundant roles in mediating platelet activation by collagen.
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pubmed:affiliation |
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK. a.c.pearce@bham.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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