ArticleBlood2010
Tyrosine kinase Btk regulates E-selectin-mediated integrin activation and neutrophil recruitment by controlling phospholipase C (PLC) gamma2 and PI3Kgamma pathways.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
What it found
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The trial behind it
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Who cites it
105 citing papers in PubMed, 158 citations in OpenAlex.
- Neutrophil Mechanosignaling Promotes Integrin Engagement With Endothelial Cells and Motility Within Inflamed Vessels.Frontiers in immunology · 2018Trial
- Silencing Bruton's tyrosine kinase in alveolar neutrophils protects mice from LPS/immune complex-induced acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2014Trial
- Porphyromonas gingivalis-derived extracellular vesicles aggravate bone destruction in rheumatoid arthritis by promoting Syk-dependent osteoclastogenesis.International journal of oral science · 2026Article
- Integrin activation by two independently regulated calcium-mediated pathways is required for neutrophil recruitment.Cell communication and signaling : CCS · 2026Article
- PLCG2 across human disease: genetic variants, signaling mechanisms, and clinical implications.Journal of translational medicine · 2026Review
- Differential Effects of Zanubrutinib and Ibrutinib on Neutrophil Antifungal Functions: Insights from Live-Cell Imaging.Journal of innate immunity · 2026Article
- Pathophysiological mechanisms and therapeutic potential of E-selectin in pulmonary arterial hypertension.Frontiers in immunology · 2026Review
- RhoA GAP Myo9b regulates β2-integrin activity and neutrophil recruitment during murine acute kidney injury.Blood · 2025Article
- Article
- Alveolar epithelial and vascular CXCR2 mediates transcytosis of CXCL1 in inflamed lungs.Nature communications · 2025Article
- STIM1/2 maintain signaling competence at ER-PM contact sites during neutrophil spreading.The Journal of cell biology · 2025Article
- From development to clinical success: the journey of established and next-generation BTK inhibitors.Investigational new drugs · 2025Review
- Inhibition of Bruton's tyrosine kinase restricts neuroinflammation following intracerebral hemorrhage.Theranostics · 2025Article
- Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2.Acta biochimica et biophysica Sinica · 2024Article
- E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8/S100A9 release from neutrophils via transient gasdermin D pore formation.Nature immunology · 2023Article
- Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach.Cell reports. Medicine · 2023Review
- Neutrophil biology in injuries and diseases of the central and peripheral nervous systems.Progress in neurobiology · 2023Review
- Cotargeting of BTK and MALT1 overcomes resistance to BTK inhibitors in mantle cell lymphoma.The Journal of clinical investigation · 2023Article
- NETosis: an emerging therapeutic target in renal diseases.Frontiers in immunology · 2023Review
- Bruton's tyrosine kinase inhibition attenuates disease progression by reducing renal immune cell invasion in mice with hemolytic-uremic syndrome.Frontiers in immunology · 2023Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Selectins mediate leukocyte rolling, trigger beta(2)-integrin activation, and promote leukocyte recruitment into inflamed tissue. E-selectin binding to P-selectin glycoprotein ligand 1 (PSGL-1) leads to activation of an immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway, which in turn activates the spleen tyrosine kinase (Syk). However, the signaling pathway linking Syk to integrin activation after E-selectin engagement is unknown. To identify the pathway, we used different gene-deficient mice in autoperfused flow chamber, intravital microscopy, peritonitis, and biochemical studies. We report here that the signaling pathway downstream of Syk divides into a phospholipase C (PLC) gamma2- and phosphoinositide 3-kinase (PI3K) gamma-dependent pathway. The Tec family kinase Bruton tyrosine kinase (Btk) is required for activating both pathways, generating inositol-3,4,5-trisphosphate (IP(3)), and inducing E-selectin-mediated slow rolling. Inhibition of this signal-transduction pathway diminished Galpha(i)-independent leukocyte adhesion to and transmigration through endothelial cells in inflamed postcapillary venules of the cremaster. Galpha(i)-independent neutrophil recruitment into the inflamed peritoneal cavity was reduced in Btk(-/-) and Plcg2(-/-) mice. Our data demonstrate the functional importance of this newly identified signaling pathway mediated by E-selectin engagement.
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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.