ArticleThe Journal of experimental medicine2003
Critical role of the carboxyl terminus of proline-rich tyrosine kinase (Pyk2) in the activation of human neutrophils by tumor necrosis factor: separation of signals for the respiratory burst and degranulation.
Article in The Journal of experimental medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 49 citations in OpenAlex.
- SKAP2 is required for defense againsteLife · 2020Article
- Therapeutic targeting of neutrophil exocytosis.Journal of leukocyte biology · 2020Review
- Three Novel Players: PTK2B, SYK, and TNFRSF21 Were Identified to Be Involved in the Regulation of Bovine Mastitis Susceptibility via GWAS and Post-transcriptional Analysis.Frontiers in immunology · 2019Article
- The pore-forming toxin listeriolysin O is degraded by neutrophil metalloproteinase-8 and fails to mediate Listeria monocytogenes intracellular survival in neutrophils.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury.Respiratory research · 2012Article
- Src-family and Syk kinases in activating and inhibitory pathways in innate immune cells: signaling cross talk.Cold Spring Harbor perspectives in biology · 2011Review
- Pyk2 is required for neutrophil degranulation and host defense responses to bacterial infection.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Downregulation of FIP200 induces apoptosis of glioblastoma cells and microvascular endothelial cells by enhancing Pyk2 activity.PloS one · 2011Article
- Recruitment of Pyk2 to SHPS-1 signaling complex is required for IGF-I-dependent mitogenic signaling in vascular smooth muscle cells.Cellular and molecular life sciences : CMLS · 2010Article
- Hematopoietic Pyk2 regulates migration of differentiated HL-60 cells.Journal of inflammation (London, England) · 2010Article
- Calcium-activated pathways and oxidative burst mediate zymosan-induced signaling and IL-10 production in human macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- Inhibition of Pyk2 blocks airway inflammation and hyperresponsiveness in a mouse model of asthma.American journal of respiratory cell and molecular biology · 2010Article
- Regulation of TNF-induced oxygen radical production in human neutrophils: role of delta-PKC.Journal of leukocyte biology · 2010Article
- The ins and outs of leukocyte integrin signaling.Annual review of immunology · 2009Review
- Dietary salt activates an endothelial proline-rich tyrosine kinase 2/c-Src/phosphatidylinositol 3-kinase complex to promote endothelial nitric oxide synthase phosphorylation.Hypertension (Dallas, Tex. : 1979) · 2008Article
- Proline-rich tyrosine kinase 2 regulates spreading and migration of eosinophils after beta2-integrin adhesion.American journal of respiratory cell and molecular biology · 2008Article
- Mechanism of dietary salt-mediated increase in intravascular production of TGF-beta1.American journal of physiology. Renal physiology · 2008Article
- Regulation of neutrophil functions by proinflammatory cytokines.International journal of hematology · 2006Review
- A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites.The Journal of clinical investigation · 2006Article
- Calcium-sensing soluble adenylyl cyclase mediates TNF signal transduction in human neutrophils.The Journal of experimental medicine · 2005Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Transduction of Tat-tagged fusion proteins confirmed a hypothesis based on pharmacologic inhibitors (Fuortes, M., M. Melchior, H. Han, G.J. Lyon, and C. Nathan. 1999. J. Clin. Invest. 104:327-335) that proline-rich tyrosine kinase (Pyk2) plays a critical role in the activation of adherent human neutrophils, and allowed an analysis of individual Pyk2 domains not possible with chemical inhibitors. Acting as a dominant negative, the COOH terminus of Pyk2 fused to a Tat peptide (Tat-CT), but not other regions of Pyk2, specifically inhibited the respiratory burst of cells responding to tumor necrosis factor (TNF), Salmonella, or Listeria, while sparing responses induced by phorbol ester. Tat-CT suppressed TNF-triggered cell spreading and the phosphorylation of endogenous Pyk2 and the associated tyrosine kinase Syk without blocking the ability of neutrophils to degranulate and kill bacteria. Thus, separate signals control the respiratory burst and degranulation, and a normal rate of killing of some bacteria can be sustained by granule products in conjunction with a minimal residual respiratory burst. Inhibition of select inflammatory functions without impairment of antibacterial activity may commend the Pyk2 pathway as a potential target for antiinflammatory therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.