Regulation of Cyr61 gene expression by mechanical stretch through multiple signaling pathways
Abstract
The cysteine-rich protein 61 (Cyr61) is a signaling molecule with functions in cell migration, adhesion, and proliferation. This protein is encoded by an immediate early gene whose expression is mainly induced by serum growth factors. Here we show that Cyr61 mRNA levels increase sharply in response to cyclic mechanical stretch applied to cultured bladder smooth muscle cells. Stretch-induced changes of Cyr61 transcripts were transient and accompanied by an increase of the encoded protein that localized mainly to the cytoplasm and nucleus of the cells. With the use of pharmacological agents that interfere with known signaling pathways, we show that transduction mechanisms involving protein kinase C and phosphatidylinositol 3-kinase activation partly blocked stretch-induced Cyr61 gene expression. Selective inhibition of Rho kinase pathways altered this stretch effect as well. Meanwhile, using inhibitors of the actin cytoskeleton, we show that Cyr61 gene expression is sensitive to mechanisms that sense actin dynamics. These results establish the regulation of Cyr61 gene by mechanical stretch and provide clues to the key signaling molecules involved in this process.
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CCN1 has been detected in the nucleus despite the absence of a classical nuclear localization signal.
“In contrast to its prominent localization to the ECM, CCN1 has also been detected in the nucleus of cells, despite the absence of a classical nuclear localization signal [93].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [93]
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- Authors
- Tamura, I., Rosenbloom, J., Macarak, E., & Chaqour, B.
- Affiliations
- University of Pennsylvania (US)
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2001-11-01
- Volume
- 281
- Issue
- 5
- Pages
- C1524-C1532
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- OpenAlex
- W2181743527
- Cited by
- 90
- References
- 50
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 7 · 2012: 2
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK002685, DK-02685, DK-45419, R01DK045419, R01DK060572)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- CYR61, gene expression regulation, mechanical stretch, bladder smooth muscle cells, protein kinase C, phosphatidylinositol 3-kinase, Rho kinase, actin cytoskeleton, actin dynamics, immediate early genes, mechanotransduction
- MeSH terms
- Animals, Benzamides, Cattle, Cells, Cultured, Electrophoresis, Polyacrylamide Gel, Enzyme Inhibitors, Female, Methionine, Muscle Spindles, Nuclear Proteins, Physical Stimulation, Blotting, Northern, DNA Probes, Signal Transduction, Gene Expression Regulation, Enzymologic, In Situ Hybridization, Phosphatidylinositol 3-Kinases
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