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Regulation of platelet-activating factor-mediated protein tyrosine phosphatase 1B activation by a Janus kinase 2/calpain pathway
- Source :
- PLoS ONE, Vol 12, Iss 7, p e0180336 (2017), PLoS ONE
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
Abstract
- Atherosclerosis is a pro-inflammatory condition underlying many cardiovascular diseases. Platelet-activating factor (PAF) and interleukin 6 (IL-6) are actively involved in the onset and progression of atherosclerotic plaques. The involvement of monocyte-derived macrophages is well characterized in the installation of inflammatory conditions in the plaque, but less is known about the contribution of monocyte-derived dendritic cells (Mo-DCs). In the same way, the involvement of calcium, phospholipase C and A2 in PAF-induced IL-6 production, in different cells types, has been shown; however, the importance of the Jak/STAT pathway and its regulation by protein-tyrosine phosphatases in this response have not been addressed. In this study, we report that PAF stimulates PTP1B activity via Jak2, thereby modulating PAF-induced IL-6 production. Using HEK 293 cells stably transfected with the PAF receptor in order to discriminate the pathway components, our results suggest that Jak2 modulates PAF-induced IL-6 production via both positive and negative pathways. Jak2 kinase activity was necessary for maximal transactivation of the IL-6 promoter, as seen by luciferase assays, whereas the same kinase also downregulated this promoter transactivation through the activation of a calcium/calpain/PTP1B pathway. The same pathways were operational in monocyte-derived dendritic cells, since PAF-induced PTP1B activation negatively regulated PAF-induced IL-6 mRNA production and, in addition, Jak2 activated calpain, one of the components involved in PAF-induced PTP1B activation. Results obtained in this study indicate that Jak2 activation is important for maximal IL-6 promoter transactivation by PAF and that PTP1B is involved in the negative regulation of this transactivation. However, PTP1B does not directly regulate Jak2 activation, but rather Jak2 regulates PAF-induced PTP1B activation.
- Subjects :
- 0301 basic medicine
Physiology
lcsh:Medicine
Biochemistry
Vascular Medicine
Ion Channels
Receptors, G-Protein-Coupled
Transactivation
Genes, Reporter
Medicine and Health Sciences
Small interfering RNAs
Post-Translational Modification
Phosphorylation
Luciferases
Promoter Regions, Genetic
lcsh:Science
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Multidisciplinary
Janus kinase 2
biology
Chemistry
Calpain
Physics
Hydrolysis
Chemical Reactions
JAK-STAT signaling pathway
Cell biology
Enzymes
Nucleic acids
Electrophysiology
Bioassays and Physiological Analysis
Physical Sciences
hormones, hormone substitutes, and hormone antagonists
Research Article
Signal Transduction
Primary Cell Culture
Biophysics
Neurophysiology
Platelet Membrane Glycoproteins
Transfection
Research and Analysis Methods
03 medical and health sciences
Genetics
Humans
c-Raf
Kinase activity
Non-coding RNA
Molecular Biology Techniques
Molecular Biology
Colorimetric Assays
MAP kinase kinase kinase
Biology and life sciences
Akt/PKB signaling pathway
Interleukin-6
Macrophages
lcsh:R
Phosphatases
Proteins
Dendritic Cells
Janus Kinase 2
Atherosclerosis
Gene regulation
030104 developmental biology
HEK293 Cells
Gene Expression Regulation
biology.protein
Enzymology
RNA
Calcium
lcsh:Q
Gene expression
Calcium Channels
Janus kinase
Biochemical Analysis
Neuroscience
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....49c63c22cf2784d8e9c9065dbf81c06d