Evidence map›Paper›PMID 20400514›Full record

ArticleThe Journal of biological chemistry2010

Cbl-b is a novel physiologic regulator of glycoprotein VI-dependent platelet activation.

James L Daniel, Carol A Dangelmaier, Sripal Mada, Lorena Buitrago, Jianguo Jin, Wallace Y Langdon, Alexander Y Tsygankov, Satya P Kunapuli, Archana Sanjay

Open access · hybridAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 27 citations in OpenAlex.

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  11. Proteasome proteolysis supports stimulated platelet function and thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2014
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

James L DanielDepartment of Anatomy, Sol Sherry Thrombosis Research Center, Temple University, Philadelphia, Pennsylvania 19140, USA. james.daniel@temple.edu
Carol A Dangelmaier
Sripal Mada
Lorena Buitrago
Jianguo Jin
Wallace Y Langdon
Alexander Y Tsygankov
Satya P Kunapuli
Archana Sanjay
Temple University · USUniversity of Western Australia · AU

Funding

MOLECULAR BASIS FOR ADP INDUCED PLATELET ACTIVATIONR01HL060683 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KUNAPULI, SATYA P. · 1998 to 2011
$3.9M
Functional G Protein pathways in platelet activationR01HL081322 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KUNAPULI, SATYA P. · 2006 to 2010
$2.9M
Regulation of Osteoclastic Bone Resorption:Role of Cb1bR01DE004724 · NIDCR · YALE UNIVERSITY · PI BARON, ROLAND E · 1985 to 2008
$2.0M
Platelet ADP ReceptorsR01HL080444 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI KUNAPULI, SATYA P. · 2005 to 2008
$1.8M
C-CBL IN MODULATION OF CELL ADHESION AND MORPHOLOGYR01CA078499 · NCI · TEMPLE UNIVERSITY · PI TSYGANKOV, ALEXANDER Y · 1998 to 2005
$1.6M
REGULATION OF OSTEOCLASTIC BONE RESORPTIONR37DE004724 · NIDCR · YALE UNIVERSITY · PI BARON, ROLAND E · 1993 to 2002
$998k
NCI NIH HHS CA78499NCI NIH HHS R01 CA078499NHLBI NIH HHS HL60683NHLBI NIH HHS HL80444NHLBI NIH HHS HL81322NHLBI NIH HHS R01 HL060683NHLBI NIH HHS R01 HL080444NHLBI NIH HHS R01 HL081322NIDCR NIH HHS DE004724NIDCR NIH HHS R01 DE004724NIDCR NIH HHS R37 DE004724
6 · The paper itself

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.

Indexed as

Gene Expression RegulationPlatelet ActivationAdaptor Proteins, Signal TransducingAgammaglobulinaemia Tyrosine KinaseAnimalsBlood PlateletsHumansLymphocyte ActivationMiceMice, Inbred C57BLMice, TransgenicPhospholipase C gammaPlatelet Membrane GlycoproteinsProtein-Tyrosine KinasesProto-Oncogene Proteins c-cblAdaptor Proteins, Signal TransducingAgammaglobulinaemia Tyrosine KinaseBTK protein, humanBtk protein, mouseCBLB protein, humanCblb protein, mousePhospholipase C gammaPlatelet Membrane Glycoproteinsplatelet membrane glycoprotein VIProtein-Tyrosine KinasesProto-Oncogene Proteins c-cbl

Identifiers

PMID20400514
PMCPMC2878491
OpenAlexW2040125992

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.