| pubmed-article:20400514 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20400514 | lifeskim:mentions | umls-concept:C0032173 | lld:lifeskim |
| pubmed-article:20400514 | lifeskim:mentions | umls-concept:C0017968 | lld:lifeskim |
| pubmed-article:20400514 | lifeskim:mentions | umls-concept:C0205463 | lld:lifeskim |
| pubmed-article:20400514 | lifeskim:mentions | umls-concept:C1704735 | lld:lifeskim |
| pubmed-article:20400514 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:20400514 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:20400514 | pubmed:issue | 23 | lld:pubmed |
| pubmed-article:20400514 | pubmed:dateCreated | 2010-5-31 | lld:pubmed |
| pubmed-article:20400514 | pubmed:abstractText | Cbl-b, a member of the Cbl family of E3 ubiquitin ligases, plays an important role in the activation of lymphocytes. However, its function in platelets remains unknown. We show that Cbl-b is expressed in human platelets along with c-Cbl, but in contrast to c-Cbl, it is not tyrosine-phosphorylated upon glycoprotein VI (GPVI) stimulation. Cbl-b, unlike c-Cbl, is not required for Syk ubiquitylation downstream of GPVI activation. Phospholipase Cgamma2 (PLCgamma2) and Bruton's tyrosine kinase (BTK) are constituently associated with Cbl-b. Cbl-b-deficient (Cbl-b(-/-)) platelets display an inhibition in the concentration-response curve for GPVI-specific agonist-induced aggregation, secretion, and Ca(2+) mobilization. A parallel inhibition is found for activation of PLCgamma2 and BTK. However, Syk activation is not affected by the absence of Cbl-b, indicating that Cbl-b acts downstream of Syk but upstream of BTK and PLCgamma2. When Cbl-b(-/-) mice were tested in the ferric chloride thrombosis model, occlusion time was increased and clot stability was reduced compared with wild type controls. These data indicate that Cbl-b plays a positive modulatory role in GPVI-dependent platelet signaling, which translates to an important regulatory role in hemostasis and thrombosis in vivo. | lld:pubmed |
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| pubmed-article:20400514 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:20400514 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:20400514 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20400514 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:20400514 | pubmed:issn | 1083-351X | lld:pubmed |
| pubmed-article:20400514 | pubmed:author | pubmed-author:JinJianguoJ | lld:pubmed |
| pubmed-article:20400514 | pubmed:author | pubmed-author:KunapuliSatya... | lld:pubmed |
| pubmed-article:20400514 | pubmed:author | pubmed-author:LangdonWallac... | lld:pubmed |
| pubmed-article:20400514 | pubmed:author | pubmed-author:DanielJames... | lld:pubmed |
| pubmed-article:20400514 | pubmed:author | pubmed-author:TsygankovAlex... | lld:pubmed |
| pubmed-article:20400514 | pubmed:author | pubmed-author:SanjayArchana... | lld:pubmed |
| pubmed-article:20400514 | pubmed:author | pubmed-author:DangelmaierCa... | lld:pubmed |
| pubmed-article:20400514 | pubmed:author | pubmed-author:BuitragoLoren... | lld:pubmed |
| pubmed-article:20400514 | pubmed:author | pubmed-author:MadaSripalS | lld:pubmed |
| pubmed-article:20400514 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20400514 | pubmed:day | 4 | lld:pubmed |
| pubmed-article:20400514 | pubmed:volume | 285 | lld:pubmed |
| pubmed-article:20400514 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20400514 | pubmed:authorsComplete | Y | lld:pubmed |
