ArticleJournal of neurochemistry2008
Protease-activated receptor dependent and independent signaling by kallikreins 1 and 6 in CNS neuron and astroglial cell lines.
Article in Journal of neurochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
- Deferasirox Derivatives as Inhibitors of Kallikrein-Related Peptidases Associated to Neurodegenerative Diseases.ChemMedChem · 2025Article
- PARting Neuroinflammation with Protease-Activated Receptor 2 Pepducins.The Journal of pharmacology and experimental therapeutics · 2024Article
- Bradykinin and Neurotensin Analogues as Potential Compounds in Colon Cancer Therapy.International journal of molecular sciences · 2023Article
- Article
- A modular map of Bradykinin-mediated inflammatory signaling network.Journal of cell communication and signaling · 2022Article
- Thrombin induces morphological and inflammatory astrocytic responses via activation of PAR1 receptor.Cell death discovery · 2022Article
- Article
- Article
- Neuroprotective Effect ofInternational journal of molecular sciences · 2020Article
- Blocking the Thrombin Receptor Promotes Repair of Demyelinated Lesions in the Adult Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Involvement of Kallikrein-Related Peptidases in Nervous System Disorders.Frontiers in cellular neuroscience · 2020Article
- Role of the protease-activated receptor 1 in regulating the function of glial cells within central and peripheral nervous system.Journal of neural transmission (Vienna, Austria : 1996) · 2019Review
- Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms.Biological chemistry · 2018Article
- The Thrombin Receptor Restricts Subventricular Zone Neural Stem Cell Expansion and Differentiation.Scientific reports · 2018Article
- Article
- Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases.International journal of molecular sciences · 2017Review
- Kallikrein-related peptidase 6 exacerbates disease in an autoimmune model of multiple sclerosis.Biological chemistry · 2016Article
- Protease-activated receptors in kidney disease progression.American journal of physiology. Renal physiology · 2016Review
- Targeting the thrombin receptor modulates inflammation and astrogliosis to improve recovery after spinal cord injury.Neurobiology of disease · 2016Article
- Kallikrein-related peptidase 8 is expressed in myocardium and induces cardiac hypertrophy.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
While protease-activated receptors (PARs) are known to mediate signaling events in CNS, contributing both to normal function and pathogenesis, the endogenous activators of CNS PARs are poorly characterized. In this study, we test the hypothesis that kallikreins (KLKs) represent an important pool of endogenous activators of CNS PARs. Specifically, KLK1 and KLK6 were examined for their ability to evoke intracellular Ca(2+) flux in a PAR-dependent fashion in NSC34 neurons and Neu7 astrocytes. Both KLKs were also examined for their ability to activate mitogen-activated protein kinases (extracellular signal-regulated kinases, C-Jun N-terminal kinases, and p38) and protein kinase B (AKT) intracellular signaling cascades. Cumulatively, these studies show that KLK6, but not KLK1, signals through PARs. KLK6 evoked intracellular Ca(2+) flux was mediated by PAR1 in neurons and both PAR1 and PAR2 in astrocytes. Importantly, both KLK1 and KLK6 altered the activation state of mitogen-activated protein kinases and AKT, suggestive of important roles for each in CNS neuron and glial differentiation, and survival. The cellular specificity of CNS-KLK activity was underscored by observations that both proteases promoted AKT activation in astrocytes, but inhibited such signaling in neurons. PAR1 and bradykinin receptor inhibitors were used to demonstrate that KLK1-mediated activation of extracellular signal-regulated kinases in neurons occurred in a non-PAR, bradykinin 2 (B2) receptor-dependent fashion, while similar signaling by KLK6 was mediated by the combined activation of PAR1 and B2. Cumulatively results indicate KLK6, but not KLK1 is an activator of CNS PARs, and that both KLKs are poised to signal in a B2 receptor-dependent fashion to regulate multiple signal transduction pathways relevant to CNS physiologic function and dysfunction.
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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.