Role of the tyrosine kinase pyk2 in the integrin-dependent activation of human neutrophils by TNF
Open Access
- 1 August 1999
- journal article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 104 (3) , 327-335
- https://doi.org/10.1172/jci6018
Abstract
Secretion of inflammatory products from neutrophils can be induced by a combination of signals from ligated integrins and receptors for soluble, physiological agonists such as TNF. Here we identify pyk2 in primary human neutrophils; localize it to focal adhesions and podosomes; and demonstrate its tyrosine phosphorylation, activation, and association with paxillin during stimulation of adherent cells by TNF. Tyrphostin A9 emerged as the most potent and selective of 51 tyrosine kinase inhibitors tested against the TNF-induced respiratory burst. Tyrphostin A9 inhibited TNF-induced tyrosine phosphorylation of pyk2 without blocking the cells’ bactericidal activity. Wortmannin, an inhibitor of phosphatidylinositol-3-kinase, potently blocked the TNF-induced respiratory burst and selectively inhibited tyrosine phosphorylation of pyk2. Thus, pyk2 appears to play an essential role in the ability of neutrophils to integrate signals from β2 integrins and TNF receptors.Keywords
This publication has 42 references indexed in Scilit:
- Tyrosine Phosphorylation of the Related Adhesion Focal Tyrosine Kinase in Megakaryocytes upon Stem Cell Factor and Phorbol Myristate Acetate Stimulation and Its Association with PaxillinJournal of Biological Chemistry, 1997
- RAFTK, a Novel Member of the Focal Adhesion Kinase Family, Is Phosphorylated and Associates with Signaling Molecules upon Activation of Mature T LymphocytesThe Journal of Experimental Medicine, 1997
- Signaling through focal adhesion kinaseBioEssays, 1997
- Constitutive activation of protein kinase B and phosphorylation of p47phox by a membrane-targeted phosphoinositide 3-kinaseCurrent Biology, 1996
- FcγRII-mediated Adhesion and Phagocytosis Induce L-Plastin Phosphorylation in Human NeutrophilsPublished by Elsevier ,1996
- Activation of SRC family kinases in human neutrophils. Evidence that p58c‐frg and p53/56lyn redistributed to a Triton X‐100‐insoluble cytoskeletal fraction, also enriched in the caveolar protein Caveolin, display an enhanced kinase activityFEBS Letters, 1996
- Discovery of a Novel, Potent, and Src Family-selective Tyrosine Kinase InhibitorJournal of Biological Chemistry, 1996
- Effect of Inhibitors of Distinct Signaling Pathways on Neutrophil O2− Generation in Response to Tumor Necrosis Factor-α, and Antibodies Against CD18 and CD11a: Evidence for a Common and Unique Pattern of Sensitivity to Wortmannin and Protein TyrosineBiochemical and Biophysical Research Communications, 1993
- Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins.The Journal of cell biology, 1989
- Neutrophil activation on biological surfaces. Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes.Journal of Clinical Investigation, 1987