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Protease-Activated Receptor Dependent and Independent Signaling by Kallikreins 1 and 6 in CNS Neuron and Astroglial Cell Lines

Title: Protease-Activated Receptor Dependent and Independent Signaling by Kallikreins 1 and 6 in CNS Neuron and Astroglial Cell Lines.
Name(s): Vandell, Alexander, author
Larson, Nadya, author
Laxmikanthan, Gurunathan, 1979-, author
Panos, Michael, author
Blaber, Sachiko, author
Blaber, Michael, author
Scarisbrick, Isobel, author
Type of Resource: text
Genre: Text
Issuance: serial
Date Issued: 2008
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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.
Identifier: FSU_migr_biomed_faculty_publications-0010 (IID)
Keywords: astrocyte, bradykinin, mitogen-activated protein kinase, neuron, protease-activated receptor, protein kinase B
Uncontrolled subjects: Animals, Astrocytes, Blotting, Western, Calcium, Cell Line, Central Nervous System, Kallikreins, Mice, Neurons, Receptors, Proteinase-Activated, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Tissue Kallikreins
Note: Originally published in Journal of Neurochemistry.
Citation: Vandell, A.G., Larson, N., Laxmikanthan, G., Panos, M., Blaber, S.I., Blaber, M. and Scarisbrick, I.A., (2008). Protease activated receptor dependent and independent signaling by kallikreins 1 and 6 in CNS neuron and astroglial cell lines. J. Neurochem. 107, 855-870.
Subject(s): Biochemistry
Molecular biology
Developmental biology
Clinical biochemistry
Medical sciences
Persistent Link to This Record:
Owner Institution: FSU
Is Part of Series: Department of Biomedical Sciences Faculty Publications.
Is Part Of: Journal of Neurochemistry.
Issue: 3, 107

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Vandell, A., Larson, N., Laxmikanthan, G., Panos, M., Blaber, S., Blaber, M., & Scarisbrick, I. (2008). Protease-Activated Receptor Dependent and Independent Signaling by Kallikreins 1 and 6 in CNS Neuron and Astroglial Cell Lines. Journal Of Neurochemistry. Retrieved from