Role of the tyrosine kinase pyk2 in the integrin-dependent activation of human neutrophils by TNF

Fuortes, M., Melchior, M., Han, H., Lyon, G. J., Nathan, C. (1999) Role of the tyrosine kinase pyk2 in the integrin-dependent activation of human neutrophils by TNF. Journal of Clinical Investigation, 104 (3). pp. 327-335. ISSN 0021-9738

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URL: http://www.ncbi.nlm.nih.gov/pubmed/10430614
DOI: 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 beta(2) integrins and TNF receptors.

Item Type: Paper
Uncontrolled Keywords: Androstadienes Cell Adhesion Cell Size Cytoskeletal Proteins Enzyme Inhibitors Focal Adhesion Kinase 2 Humans Integrins Neutrophil Activation Neutrophils Paxillin Phosphoprotein Phosphatases Phosphoproteins Phosphorylation Protein-Tyrosine Kinases Tetradecanoylphorbol Acetate Tumor Necrosis Factor-alpha Tyrosine Tyrphostins
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > cytoskeletal proteins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > integrin
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase
CSHL Authors:
Communities: CSHL labs > Lyon lab
Depositing User: Kathleen Darby
Date Deposited: 28 Apr 2014 14:39
Last Modified: 28 Apr 2014 14:39
PMCID: PMC408415
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29833

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