Evidence map›Paper›PMID 40779559›Full record

ArticleBlood advances2025

Phosphorylation at Y317 on Syk negatively regulates both ITAM- and hemITAM-mediated signaling and function in platelets.

Manal A Elzoheiry, Carol A Dangelmaier, Dhruv N Vajipayajula, Monica N Wright, Alexander Y Tsygankov, Satya P Kunapuli

Abstract read
In one paragraph

Article in Blood advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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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

1 citing paper in PubMed.

  1. Review
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

6 authors.

Manal A ElzoheirySol Sherry Thrombosis Research Center and Department of Cardiovascular Diseases, Lewis Katz School of Medicine, Temple University, Philadelphia, PA.ORCID 0000-0002-5756-3651
Carol A DangelmaierSol Sherry Thrombosis Research Center and Department of Cardiovascular Diseases, Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Dhruv N VajipayajulaSol Sherry Thrombosis Research Center and Department of Cardiovascular Diseases, Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Monica N WrightSol Sherry Thrombosis Research Center and Department of Cardiovascular Diseases, Lewis Katz School of Medicine, Temple University, Philadelphia, PA.
Alexander Y TsygankovSol Sherry Thrombosis Research Center and Department of Cardiovascular Diseases, Lewis Katz School of Medicine, Temple University, Philadelphia, PA.ORCID 0000-0002-2778-2909
Satya P KunapuliSol Sherry Thrombosis Research Center and Department of Cardiovascular Diseases, Lewis Katz School of Medicine, Temple University, Philadelphia, PA.ORCID 0000-0002-1298-3214

Funding

Novel signaling molecules regulating platelet activationR35HL155694 · NHLBI · TEMPLE UNIV OF THE COMMONWEALTH · PI Satya P. Kunapuli · 2021 to 2026
$5.6M
NHLBI NIH HHS R35 HL155694
6 · The paper itself

Abstract

abstractSpleen tyrosine kinase (Syk) is expressed in a variety of hematopoietic cells. Its phosphorylation regulates downstream signaling events upon stimulation of receptors containing an immunoreceptor tyrosine-based activation motif (ITAM), like glycoprotein VI, or a hemITAM, including the C-type lectin-like receptor 2 (CLEC-2). This study focuses on the role of a specific phosphorylation site, tyrosine 317, in the regulation of Syk function. Tyrosine 317 is located in the linker region of Syk that separates the amino-terminal, tandem pair of SH2 domains from the carboxyl-terminal catalytic domain. The amino acid sequence surrounding phosphotyrosine 317 binds to the matching recognition sequence in the tyrosine kinase-binding domain of Cbl, an E3 ubiquitin-protein ligase. To evaluate the function of this phosphorylation site, we generated mice expressing Syk(Y317F) using the CRISPR/Cas9 technique. Platelets from homozygous Syk(Y317F) mice showed enhancement of platelet signaling and physiological responses after stimulation with collagen-related peptide (CRP) and CLEC-2 cross-linking. This enhancement did not occur after stimulation with AYPGKF, a protease-activated receptor 4 agonist, or 2-methylthioadenosine diphosphate, a purinergic agonist. CRP- or CLEC-2 monoclonal antibody-induced downstream signaling events, including phosphorylation of LAT and phospholipase C γ2, were enhanced in Syk(Y317F) platelets compared with platelets from wild-type (WT) littermates. Besides an increase in platelet responses in vitro, the time to occlusion in the FeCl3 injury model was decreased in Syk(Y317F) mice compared with WT littermates. However, there was no significant difference in the tail bleeding times. Taken together, these data reveal that tyrosine 317 negatively regulates Syk signaling and functions in mouse platelets.

Indexed as

Blood PlateletsImmunoreceptor Tyrosine-Based Activation MotifSignal TransductionSyk KinaseAnimalsHumansLectins, C-TypeMicePhosphorylationLectins, C-TypeSyk KinaseSyk protein, mouse

Identifiers

PMID40779559
PMCPMC12630359

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.