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TULA-2 Deficiency Enhances Platelet Functional Responses to CLEC-2 Agonists.
Kostyak, John C; Mauri, Benjamin R; Dangelmaier, Carol; Patel, Akruti; Zhou, Yuhang; Eble, Johannes A; Tsygankov, Alexander Y; McKenzie, Steven E; Kunapuli, Satya P.
Afiliación
  • Kostyak JC; Sol Sherry Thrombosis Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States.
  • Mauri BR; Sol Sherry Thrombosis Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States.
  • Dangelmaier C; Sol Sherry Thrombosis Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States.
  • Patel A; Sol Sherry Thrombosis Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States.
  • Zhou Y; Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States.
  • Eble JA; Institute of Physiological Chemistry and Pathobiochemistry, University of Munster, Waldeyerstasse, Munster, Germany.
  • Tsygankov AY; Sol Sherry Thrombosis Research Center, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States.
  • McKenzie SE; Department of Immunology and Microbiology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States.
  • Kunapuli SP; Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, United States.
TH Open ; 2(4): e411-e419, 2018 Oct.
Article en En | MEDLINE | ID: mdl-31249969
Platelet activation is essential for hemostasis. Central to platelet activation are the signals transmitted through surface receptors such as glycoprotein VI, the protease-activated receptors, and C-type lectin-like receptor 2 (CLEC-2). CLEC-2 is a HemITAM (hem-immunoreceptor tyrosine activation motif)-bearing receptor that binds podoplanin and signals through spleen tyrosine kinase (Syk). T-cell ubiquitin ligand-2 (TULA-2) is a protein tyrosine phosphatase that is highly expressed in platelets and targets phosphorylated Y352 of Syk. We wanted to determine whether TULA-2 regulates Syk phosphorylation and activity downstream of CLEC-2. To that end, we used TULA-2 knockout mice and wild-type (WT) littermate controls. We found that TULA-2 deficiency enhances the aggregation and secretion response following stimulation with an excitatory CLEC-2 antibody or the CLEC-2 agonist rhodocytin. Consistently, Syk phosphorylation of Y346 is enhanced, as well as phosphorylation of the downstream signaling molecule PLCγ2, in TULA-2 knockout platelets treated with either CLEC-2 antibody or rhodocytin, compared with WT control platelets. Furthermore, the kinetics of Syk phosphorylation, as well as that of PLCγ2 and SLP-76, is enhanced in TULA-2 knockout platelets treated with 2.5-µg/mL CLEC-2 antibody compared with WT platelets. Similarly, thromboxane production was enhanced, in both amount and kinetics, in TULA-2 -/- platelets treated with 2.5-µg/mL CLEC-2 antibody. TULA-2 acts as a negative regulator of CLEC-2 signaling by dephosphorylating Syk on Y346 and restraining subsequent Syk-mediated signaling.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: TH Open Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: TH Open Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania