ArticleScientific reports2019
FAK and Pyk2 activity promote TNF-α and IL-1β-mediated pro-inflammatory gene expression and vascular inflammation.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Macrophage-associated kinase signaling in atherosclerosis - a systematic review.Cell communication and signaling : CCS · 2026Pooled it
- Biomarkers and Endothelial Damage in Obesity: An Insight into the Pharmacological Modulation.International journal of molecular sciences · 2026Review
- Identifying ICAM-1 as a Therapeutic Target for Cytokine Storm in Human Macrophages Through Integrative Bioinformatics Approaches.Molecules (Basel, Switzerland) · 2026Article
- The focal adhesion kinases regulate leptin action and the weight reducing effect of HDAC6 inhibition.Nature communications · 2026Article
- The loss of glycoprotein nonmetastatic melanoma protein B (GPNMB) alters endothelial cell permeability, metabolism, and survival during infectious challenge.Clinical science (London, England : 1979) · 2026Article
- Lycorine Attenuates Cardiac Fibrosis Through the Regulation of PYK2 Expression and Activity.Cardiovascular therapeutics · 2026Article
- The PKC/NOX/ROS and PYK2/MEK/ERK/PARP signalling pathways drive TRPM2 channel activation induced by non-cytolytic oxidative stress in microglial cells.Redox report : communications in free radical research · 2025Article
- Circulating cell-free RNA signatures for the characterization and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Focal adhesion kinase mediates microvascular leakage and endothelial barrier dysfunction in ischemia-reperfusion injury.Microvascular research · 2025Article
- Transcriptomic profiles in major depressive disorder: the role of immunometabolic and cell-cycle-related pathways in depression with different levels of inflammation.Molecular psychiatry · 2025Observational
- Exploring the anti-inflammatory effects of phytochemicals in attenuating interstitial cystitis-a literature review.Frontiers in pharmacology · 2025Review
- Research progress of PYK2 in digestive system diseases.Frontiers in immunology · 2025Review
- Heme oxygenase-1 modulates CD62E-dependent endothelial cell-monocyte interactions and mitigates HLA-I-induced transplant vasculopathy in mice.Frontiers in immunology · 2025Article
- The integrin adhesome and control of anti-tumour immunity.Biochemical Society transactions · 2024Review
- Molecular Mechanisms Underlying Amyloid Beta Peptide Mediated Upregulation of Vascular Cell Adhesion Molecule-1 in Alzheimer Disease.The Journal of pharmacology and experimental therapeutics · 2024Article
- Noncanonical functions of adhesion proteins in inflammation.American journal of physiology. Cell physiology · 2024Review
- The Exacerbating Effects of the Tumor Necrosis Factor in Cardiovascular Stenosis: Intimal Hyperplasia.Cancers · 2024Review
- NF-κB affected the serum levels of TNF-α and IL-1β via activation of the MAPK/NF-κB signaling pathway in rat model of acute pulmonary microthromboembolism.Pulmonary circulation · 2024Article
- Proteomics associated with coronary high-risk plaques by optical coherence tomography.Journal of thrombosis and thrombolysis · 2024Article
- FAK Family Kinases: A Potential Therapeutic Target for Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Protein tyrosine kinase (PTK) activity has been implicated in pro-inflammatory gene expression following tumor necrosis factor-α (TNF-α) or interkeukin-1β (IL-1β) stimulation. However, the identity of responsible PTK(s) in cytokine signaling have not been elucidated. To evaluate which PTK is critical to promote the cytokine-induced inflammatory cell adhesion molecule (CAM) expression including VCAM-1, ICAM-1, and E-selectin in human aortic endothelial cells (HAoECs), we have tested pharmacological inhibitors of major PTKs: Src and the focal adhesion kinase (FAK) family kinases - FAK and proline-rich tyrosine kinase (Pyk2). We found that a dual inhibitor of FAK/Pyk2 (PF-271) most effectively reduced all three CAMs upon TNF-α or IL-1β stimulation compared to FAK or Src specific inhibitors (PF-228 or Dasatinib), which inhibited only VCAM-1 expression. In vitro inflammation assays showed PF-271 reduced monocyte attachment and transmigration on HAoECs. Furthermore, FAK/Pyk2 activity was not limited to CAM expression but was also required for expression of various pro-inflammatory molecules including MCP-1 and IP-10. Both TNF-α and IL-1β signaling requires FAK/Pyk2 activity to activate ERK and JNK MAPKs leading to inflammatory gene expression. Knockdown of either FAK or Pyk2 reduced TNF-α-stimulated ERK and JNK activation and CAM expression, suggesting that activation of ERK or JNK is specific through FAK and Pyk2. Finally, FAK/Pyk2 activity is required for VCAM-1 expression and macrophage recruitment to the vessel wall in a carotid ligation model in ApoE-/- mice. Our findings define critical roles of FAK/Pyk2 in mediating inflammatory cytokine signaling and implicate FAK/Pyk2 inhibitors as potential therapeutic agents to treat vascular inflammatory disease such as atherosclerosis.
Indexed as
Identifiers
What OpenQuestion holds
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.