ArticleThe Journal of biological chemistry2010
Cbl-b is a novel physiologic regulator of glycoprotein VI-dependent platelet activation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Phosphorylation of (Ser 291) in the linker insert of Syk negatively regulates ITAM signaling in platelets.Platelets · 2024Article
- Identification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism.Scientific reports · 2021Article
- Establishment of a megakaryoblastic cell line for conventional assessment of platelet calcium signaling.International journal of hematology · 2020Article
- Role of GRK6 in the Regulation of Platelet Activation through Selective G Protein-Coupled Receptor (GPCR) Desensitization.International journal of molecular sciences · 2020Article
- Impaired Glycoprotein VI-Mediated Signaling and Platelet Functional Responses in CD45 Knockout Mice.Thrombosis and haemostasis · 2019Article
- Ascorbic acid improves thrombotic function of platelets during living donor liver transplantation by modulating the function of the E3 ubiquitin ligases c-Cbl and Cbl-b.The Journal of international medical research · 2019Article
- ELMO1 deficiency enhances platelet function.Blood advances · 2019Article
- TC21/RRas2 regulates glycoprotein VI-FcRγ-mediated platelet activation and thrombus stability.Journal of thrombosis and haemostasis : JTH · 2018Article
- A high-density immunoblotting methodology for quantification of total protein levels and phosphorylation modifications.Scientific reports · 2015Article
- MALT1-ubiquitination triggers non-genomic NF-κB/IKK signaling upon platelet activation.PloS one · 2015Article
- Proteasome proteolysis supports stimulated platelet function and thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2014Article
- RhoG protein regulates glycoprotein VI-Fc receptor γ-chain complex-mediated platelet activation and thrombus formation.The Journal of biological chemistry · 2013Article
- Tyrosine phosphorylated c-Cbl regulates platelet functional responses mediated by outside-in signaling.Blood · 2011Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.