https://doi.org/10.4081/btvb.2023.93

Restrained glycoprotein VI-induced platelet signaling by tyrosine protein phosphatases independent of phospholipase Cγ2

Vol. 2 No. 3 (2023)
Submitted: 18 July 2023
Accepted: 23 September 2023
Published: 11 October 2023
Glycoprotein VI, tyrosine kinase, platelet signaling, tyrosine phosphatase, hemostasis
Abstract Views: 232
PDF: 76
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Authors

  • Jingnan Huang https://orcid.org/0000-0001-6471-8693 Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela, and Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, Spain; Cardiovascular Research Institute Maastricht, Department of Biochemistry, Maastricht University, Netherlands.
  • Delia I. Fernández https://orcid.org/0000-0002-5055-9019 Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela, and Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, Spain; Cardiovascular Research Institute Maastricht, Department of Biochemistry, Maastricht University, Netherlands.
  • Jinmi Zou https://orcid.org/0009-0003-2179-740X Cardiovascular Research Institute Maastricht, Department of Biochemistry, Maastricht University; Synapse Research Institute, Maastricht, Netherlands.
  • Xueqing Wang Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela, and Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, Spain.
  • Johan W.M. Heemskerk • j.heemskerk@thrombin.com Synapse Research Institute, Maastricht, Netherlands.
  • Ángel García Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases, Universidade de Santiago de Compostela, and Instituto de Investigación Sanitaria de Santiago, Santiago de Compostela, Spain.

The platelet collagen receptor glycoprotein VI (GPVI) signals to activation of phospholipase Cγ2 (PLCγ2) and phosphoinositide 3-kinases (PI3K), causing platelet activation and aggregation. The non-receptor Src homology tyrosine phosphatases Shp1/2 modulate GPVI signaling in partly opposite ways, both of which are targeted by the potential drug NSC87877. Effect measurements of the Shp1/2 inhibitor NSC87877 on platelet activation via GPVI using light transmission aggregometry, Ca2+ flux assay, western blotting and flow cytometry. Effect measurements of selective PI3K inhibitor TGX221. Inhibition of Shp1/2 with NSC87877 enhanced platelet aggregation induced by the GPVI agonist, collagen-related peptide (CRP). Furthermore, NSC87877 antagonized the effects of PI3Kb inhibition, but not of Btk inhibition. Both NSC87877 and TGX221 suppressed the CRP-induced phosphorylation of PLCγ2 at activation site Tyr759. These findings indicate that drug interference of the two phosphatases Shp1/2 subtly enhances GPVI-induced platelet responses via a mechanism not involving PLCγ2 activation, even upon PI3K inhibition.

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Supporting Agencies

EU Horizon 2020 grant no. 766118

How to Cite

Huang, J., Fernández, D. I., Zou, J., Wang, X., Heemskerk, J. W., & García, Ángel. (2023). Restrained glycoprotein VI-induced platelet signaling by tyrosine protein phosphatases independent of phospholipase Cγ2. Bleeding, Thrombosis and Vascular Biology, 2(3). https://doi.org/10.4081/btvb.2023.93
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