ArticleThe Journal of biological chemistry2010
Plasma kallikrein promotes epidermal growth factor receptor transactivation and signaling in vascular smooth muscle through direct activation of protease-activated receptors.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 30 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review.BioMed research international · 2016Pooled it
- A disintegrin-like and metalloproteinase 15 facilitates glioblastoma proliferation and metastasis through activation of the protease-activated receptor 1.CytoJournal · 2025Article
- Endothelial protease-activated receptor 4: impotent or important?Frontiers in cardiovascular medicine · 2025Review
- Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond.Frontiers in physiology · 2023Review
- 6-(Arylaminomethyl) Isoquinolines as Enzyme Inhibitors and Their Preparation: A Patent Highlight of Factor XIIa Inhibitors.Cardiovascular & hematological agents in medicinal chemistry · 2023Article
- Molecular Dambusters: What Is Behind Hyperpermeability in Bradykinin-Mediated Angioedema?Clinical reviews in allergy & immunology · 2021Review
- Modulation of Neuro-Inflammatory Signals in Microglia by Plasma Prekallikrein and Neuronal Cell Debris.Frontiers in pharmacology · 2021Article
- Plasma Kallikrein as a Modulator of Liver Injury/Remodeling.Frontiers in pharmacology · 2021Article
- Activation of Kinin B1R Upregulates ADAM17 and Results in ACE2 Shedding in Neurons.International journal of molecular sciences · 2020Article
- Article
- Role of protease-activated receptor 2 in regulation of renin synthesis and secretion in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2019Article
- Plasma kallikrein modulates immune cell trafficking during neuroinflammation via PAR2 and bradykinin release.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Identification and pharmaceutical evaluation of novel frog skin-derived serine proteinase inhibitor peptide-PE-BBI (Pelophylax esculentus Bowman-Birk inhibitor) for the potential treatment of cancer.Scientific reports · 2018Article
- The Plasma Kallikrein-Kininogen Pathway Is Critical in the Pathogenesis of Colitis in Mice.Frontiers in immunology · 2018Article
- A critical role for plasma kallikrein in the pathogenesis of autoantibody-induced arthritis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Danhong injection reduces vascular remodeling and up-regulates the Kallikrein-kinin system in spontaneously hypertensive rats.Scientific reports · 2017Article
- Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP.Biochimie · 2017Article
- Recent Progress in Research on the Pathogenesis of Pulmonary Thromboembolism: An Old Story with New Perspectives.BioMed research international · 2017Review
- Kallikreins - The melting pot of activity and function.Biochimie · 2016Review
- Plasma Prekallikrein Is Associated With Carotid Intima-Media Thickness in Type 1 Diabetes.Diabetes · 2016Observational
Corrections and comments
- Correction · 2011-07-01Concerns/Issues about Authorship/Affiliation · · Hesham M. El-Shewy was initially left off the author list;
- Erratum issuedEl-Shewy, Hesham M [added]
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The kallikrein-kinin system, along with the interlocking renin-angiotensin system, is a key regulator of vascular contractility and injury response. The principal effectors of the kallikrein-kinin system are plasma and tissue kallikreins, proteases that cleave high molecular weight kininogen to produce bradykinin. Most of the cellular actions of kallikrein (KK) are thought to be mediated by bradykinin, which acts via G protein-coupled B1 and B2 bradykinin receptors on VSMCs and endothelial cells. Here, we find that primary aortic vascular smooth muscle but not endothelial cells possess the ability to activate plasma prekallikrein. Surprisingly, exposing VSMCs to prekallikrein leads to activation of the ERK1/2 mitogen-activated protein kinase cascade via a mechanism that requires kallikrein activity but does not involve bradykinin receptors. In transfected HEK293 cells, we find that plasma kallikrein directly activates G protein-coupled protease-activated receptors (PARs) 1 and 2, which possess consensus kallikrein cleavage sites, but not PAR4. In vascular smooth muscles, KK stimulates ADAM (a disintegrin and metalloprotease) 17 activity via a PAR1/2 receptor-dependent mechanism, leading sequentially to release of the endogenous ADAM17 substrates, amphiregulin and tumor necrosis factor-α, metalloprotease-dependent transactivation of epidermal growth factor receptors, and metalloprotease and epidermal growth factor receptor-dependent ERK1/2 activation. These results suggest a novel mechanism of bradykinin-independent kallikrein action that may contribute to the regulation of vascular responses in pathophysiologic states, such as diabetes mellitus.
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.