ArticleThe Journal of experimental medicine2002
Constitutive activation of the SRC family kinase Hck results in spontaneous pulmonary inflammation and an enhanced innate immune response.
Article in The Journal of experimental medicine, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Genomic Analysis of Kidney Allograft Injury Identifies Hematopoietic Cell Kinase as a Key Driver of Renal Fibrosis.Journal of the American Society of Nephrology : JASN · 2017Pooled it
- The Src-Family Kinases Hck, Fgr and Lyn Drive Immune Complex-Mediated Glomerulonephritis Through the Syk Tyrosine Kinase.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- RAS P21 Protein Activator 3 finetunes Type I immunity by limiting HCK-mediated STAT4 phosphorylation.Nature communications · 2026Article
- Hematopoietic cell kinase regulates microglial/macrophage activation to drive neuroinflammation after traumatic brain injury.Cell communication and signaling : CCS · 2026Article
- Expanding the Spectrum of Src-Family Kinase-Related Autoinflammatory Diseases: Monogenic Vasculitis Caused By Germline Pathogenic Variants in HCK and FGR.Journal of clinical immunology · 2026Article
- Novel HCK-associated mutation causing autoinflammatory disorder with pulmonary manifestations in a pediatric patient.Pediatric rheumatology online journal · 2025Article
- An unconventional T cell nexus drives HCK-mediated chronic obstructive pulmonary disease in mice.EBioMedicine · 2025Article
- Identification of key genes in membranous nephropathy and non-alcoholic fatty liver disease by bioinformatics and machine learning.Frontiers in immunology · 2025Article
- The dual HCK/BTK inhibitor KIN-8194 impairs growth and integrin-mediated adhesion of BTKi-resistant mantle cell lymphoma.Leukemia · 2024Article
- Urinary TYROBP and HCK as genetic biomarkers for non-invasive diagnosis and therapeutic targeting in IgA nephropathy.Frontiers in genetics · 2024Article
- Molecular and metabolic regulation of immunosuppression in metastatic pancreatic ductal adenocarcinoma.Molecular cancer · 2023Review
- HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy.Nature communications · 2023Article
- Myeloid Src-family kinases are critical for neutrophil-mediated autoinflammation in gout and motheaten models.The Journal of experimental medicine · 2023Article
- Development of genomic phenotype and immunophenotype of acute respiratory distress syndrome using autophagy and metabolism-related genes.Frontiers in immunology · 2023Article
- Inhibition of HCK in myeloid cells restricts pancreatic tumor growth and metastasis.Cell reports · 2022Article
- Therapeutic inhibition of the SRC-kinase HCK facilitates T cell tumor infiltration and improves response to immunotherapy.Science advances · 2022Article
- Bioinformatics analysis identifies immune-related gene signatures and subtypes in diabetic nephropathy.Frontiers in endocrinology · 2022Article
- HCK is a Potential Prognostic Biomarker that Correlates with Immune Cell Infiltration in Acute Myeloid Leukemia.Disease markers · 2022Article
- Use of a Network-Based Method to Identify Latent Genes Associated with Hearing Loss in Children.Frontiers in cell and developmental biology · 2021Article
- Identification of the Main Active Components and Mechanism of Wang Bi Tablet in Treating Rheumatoid Arthritis Based on Integrative Pharmacology.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To identify the physiological role of Hck, a functionally redundant member of the Src family of tyrosine kinases expressed in myelomonocytic cells, we generated Hck(F/F) "knock-in" mice which carry a targeted tyrosine (Y) to phenylalanine (F) substitution of the COOH-terminal, negative regulatory Y(499)-residue in the Hck protein. Unlike their Hck(-/-) "loss-of-function" counterparts, Hck(F/F) "gain-of-function" mice spontaneously acquired a lung pathology characterized by extensive eosinophilic and mononuclear cell infiltration within the lung parenchyma, alveolar airspaces, and around blood vessels, as well as marked epithelial mucus metaplasia in conducting airways. Lungs from Hck(F/F) mice showed areas of mild emphysema and pulmonary fibrosis, which together with inflammation resulted in altered lung function and respiratory distress in aging mice. When challenged transnasally with lipopolysaccharide (LPS), Hck(F/F) mice displayed an exaggerated pulmonary innate immune response, characterized by excessive release of matrix metalloproteinases and tumor necrosis factor (TNF)alpha. Similarly, Hck(F/F) mice were highly sensitive to endotoxemia after systemic administration of LPS, and macrophages and neutrophils derived from Hck(F/F) mice exhibited enhanced effector functions in vitro (e.g., nitric oxide and TNFalpha production, chemotaxis, and degranulation). Based on the demonstrated functional association of Hck with leukocyte integrins, we propose that constitutive activation of Hck may mimic adhesion-dependent priming of leukocytes. Thus, our observations collectively suggest an enhanced innate immune response in Hck(F/F) mice thereby skewing innate immunity from a reversible physiological host defense response to one causing irreversible tissue damage.
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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.