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A new role for proline‐rich tyrosine kinase 2 (Pyk2) in polymorphonuclear leukocyte adhesive responses triggered by P‐selectin
Author(s) -
Federico Lorenzo,
Manarini Stefano,
Panchatcharam Manikandan,
Pamuklar Zehra,
Rojas Mauricio,
Evangelista Virgilio,
Smyth Susan S
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a225-a
Subject(s) - platelet , chemistry , phosphorylation , proto oncogene tyrosine protein kinase src , adhesion , tyrosine phosphorylation , platelet activation , microbiology and biotechnology , p selectin , platelet adhesiveness , tyrosine kinase , immunology , medicine , receptor , biochemistry , biology , platelet aggregation , organic chemistry
After percutaneous coronary intervention, circulating leukocytes physically and functionally interact with adherent platelets at sites of vascular damage and significantly contribute to intimal hyperplasia. Adhesion of PMNs to activated platelets is coordinated by an adhesion cascade in which platelet P‐selectin binds to P‐selectin glycoprotein ligand‐1 (PSGL‐1)on leukocytes to promote tethering and subsequent β2integrin/Src‐dependent firm adhesion. The aim of this study was to investigate the role of Pyk2 in PMN upon platelet/Pselectin‐dependent interactions. P‐selectin stimulated homotypic PMN aggregation accompanied by significant increases in β2integrin/Src‐dependent Pyk2 tyrosine phosphorylation. TyrphostinA9, a Pyk2 inhibitor, dose‐dependently decreased Pyk2 phosphorylation and PMN responses. Similar results were observed with rolipram, a specific PDE4 inhibitor, with inhibition of Pyk2 activity correlating with lack of PMN adhesive response. Rolipram significantly decreased PMN recruitment by platelets following femoral artery injury in mice. In conclusion, we propose that Pyk2 is a potential mediator of PMN‐platelet interactions and may be a novel molecular target for treatment and prevention of their pathological consequences. Support NIH R01HL078663