ArticleBlood2020
Interplay between the tyrosine kinases Chk and Csk and phosphatase PTPRJ is critical for regulating platelets in mice.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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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.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Synergistic effects of deleting the tyrosine phosphatases Shp1 and Shp2 on megakaryopoiesis and thrombopoiesis in mice.bioRxiv : the preprint server for biology · 2025Article
- Effect of antiplatelet agents and tyrosine kinase inhibitors on oxLDL-mediated procoagulant platelet activity.Blood advances · 2023Article
- Editorial: Regulation and dysfunction of CSK and CHK.Frontiers in cell and developmental biology · 2023Article
- Regulation, targets and functions of CSK.Frontiers in cell and developmental biology · 2023Review
- Review
- Platelets and tyrosine kinase inhibitors: clinical features, mechanisms of action, and effects on physiology.American journal of physiology. Cell physiology · 2022Review
- The dosing of ibrutinib and related Bruton's tyrosine kinase inhibitors: eliminating the use of brute force.Blood advances · 2022Article
- GRK2 regulates ADP signaling in platelets via P2Y1 and P2Y12.Blood advances · 2022Article
- G6b-B regulates an essential step in megakaryocyte maturation.Blood advances · 2022Article
- Characterization of the Role of Integrin α5β1 in Platelet Function, Hemostasis, and Experimental Thrombosis.Thrombosis and haemostasis · 2022Article
- Hereditable variants of classical protein tyrosine phosphatase genes: Will they prove innocent or guilty?Frontiers in cell and developmental biology · 2022Review
- Platelet Src family kinases: A tale of reversible phosphorylation.Research and practice in thrombosis and haemostasis · 2021Review
- CHK Methylation Is Elevated in Colon Cancer Cells and Contributes to the Oncogenic Properties.Frontiers in cell and developmental biology · 2021Article
- Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress.Research and practice in thrombosis and haemostasis · 2020Article
- Article
- Identification of Potential Biomarkers and Immune Features of Sepsis Using Bioinformatics Analysis.Mediators of inflammation · 2020Article
- Role of Rho-GTPases in megakaryopoiesis.Small GTPasesReview
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
The Src family kinases (SFKs) Src, Lyn, and Fyn are essential for platelet activation and also involved in megakaryocyte (MK) development and platelet production. Platelet SFKs are inhibited by C-terminal Src kinase (Csk), which phosphorylates a conserved tyrosine in their C-terminal tail, and are activated by the receptor-type tyrosine phosphatase PTPRJ (CD148, DEP-1), which dephosphorylates the same residue. Deletion of Csk and PTPRJ in the MK lineage in mice results in increased SFK activity, but paradoxically hypoactive platelets resulting from negative feedback mechanisms, including upregulation of Csk homologous kinase (Chk) expression. Here, we investigate the role of Chk in platelets, functional redundancy with Csk, and the physiological consequences of ablating Chk, Csk, and PTPRJ in mice. Platelet count was normal in Chk knockout (KO) mice, reduced by 92% in Chk;Csk double KO (DKO) mice, and partially rescued in Chk;Csk;Ptprj triple KO (TKO) mice. Megakaryocyte numbers were significantly increased in both DKO and TKO mice. Phosphorylation of the inhibitory tyrosine of SFKs was almost completely abolished in DKO platelets, which was partially rescued in Src and Fyn in TKO platelets. This residual phosphorylation was abolished by Src inhibitors, revealing an unexpected mechanism in which SFKs autoinhibit their activity by phosphorylating their C-terminal tyrosine residues. We demonstrate that reduced inhibitory phosphorylation of SFKs leads to thrombocytopenia, with Csk being the dominant inhibitor in platelets and Chk having an auxiliary role. PTPRJ deletion in addition to Chk and Csk ameliorates the extent of thrombocytopenia, suggesting targeting it may have therapeutic benefits in such conditions.
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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 Socratic graph.