ArticleJournal of immunology (Baltimore, Md. : 1950)2007
The Src family kinases Hck and Fgr regulate neutrophil responses to N-formyl-methionyl-leucyl-phenylalanine.
Article in Journal of immunology (Baltimore, Md. : 1950), 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 102 citations in OpenAlex.
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- Extraction of Innate Immune Genes in Dairy Cattle and the Regulation of Their Expression in Early Embryos.Genes · 2024Review
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- HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy.Nature communications · 2023Article
- ATG5 provides host protection acting as a switch in the atg8ylation cascade between autophagy and secretion.Developmental cell · 2023Article
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- Abnormal neutrophil polarization in chronic obstructive pulmonary disease and how cigarette smoke extracts attract neutrophils.Annals of translational medicine · 2022Article
- A Model for the Signal Initiation Complex Between Arrestin-3 and the Src Family Kinase Fgr.Journal of molecular biology · 2022Article
- GPCRs thatSmall GTPases · 2022Review
- Bletinib ameliorates neutrophilic inflammation and lung injury by inhibiting Src family kinase phosphorylation and activity.British journal of pharmacology · 2021Article
- Regulation of macrophage functions by FABP-mediated inflammatory and metabolic pathways.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Review
- Biomimetic nanotherapy: core-shell structured nanocomplexes based on the neutrophil membrane for targeted therapy of lymphoma.Journal of nanobiotechnology · 2021Article
- Staphylococcus aureus Panton-Valentine Leukocidin triggers an alternative NETosis process targeting mitochondria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Src kinase inhibition with dasatinib impairs neutrophil function and clearance of Escherichia coli infection in a murine model of acute lung injury.Journal of inflammation (London, England) · 2020Article
- Phosphoproteomic Analysis of Rat Neutrophils Shows the Effect of Intestinal Ischemia/Reperfusion and Preconditioning on Kinases and Phosphatases.International journal of molecular sciences · 2020Article
- Src family kinase-mediated vesicle trafficking is critical for neutrophil basement membrane penetration.Haematologica · 2020Article
- SKAP2 is required for defense againsteLife · 2020Article
- CEACAM3-A Prim(at)e Invention for Opsonin-Independent Phagocytosis of Bacteria.Frontiers in immunology · 2019Review
- Phospholipid transfer protein and alpha-1 antitrypsin regulate Hck kinase activity during neutrophil degranulation.Scientific reports · 2018Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The chemotactic peptide formyl-methionyl-leucyl-phenilalanine (fMLP) triggers intracellular protein tyrosine phosphorylation leading to neutrophil activation. Deficiency of the Src family kinases Hck and Fgr have previously been found to regulate fMLP-induced degranulation. In this study, we further investigate fMLP signaling in hck-/-fgr-/- neutrophils and find that they fail to activate a respiratory burst and display reduced F-actin polymerization in response to fMLP. Additionally, albeit migration of both hck-/-fgr-/-mouse neutrophils and human neutrophils incubated with the Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) through 3-microm pore size Transwells was normal, deficiency, or inhibition, of Src kinases resulted in a failure of neutrophils to migrate through 1-microm pore size Transwells. Among MAPKs, phosphorylation of ERK1/2 was not different, phosphorylation of p38 was only partially affected, and phosphorylation of JNK was markedly decreased in fMLP-stimulated hck-/-fgr-/- neutrophils and in human neutrophils incubated with PP2. An increase in intracellular Ca(2+) concentration and phosphorylation of Akt/PKB occurred normally in fMLP-stimulated hck-/-fgr-/- neutrophils, indicating that activation of both phosphoinositide-specific phospholipase C and PI3K is independent of Hck and Fgr. In contrast, phosphorylation of the Rho/Rac guanine nucleotide exchange factor Vav1 and the Rac target p21-activated kinases were markedly reduced in both hck-/-fgr-/- neutrophils and human neutrophils incubated with a PP2. Consistent with these findings, PP2 inhibited Rac2 activation in human neutrophils. We suggest that Hck and Fgr act within a signaling pathway triggered by fMLP receptors that involves Vav1 and p21-activated kinases, leading to respiratory burst and F-actin polymerization.
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Registered trials
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