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Thrombin Inactivates Myosin Light Chain Phosphatase via Rho and Its Target Rho Kinase in Human Endothelial Cells
Open accessAbstract
The role of Rho GTPase and its downstream targets Rho kinase and myosin light chain phosphatase in thrombin-induced endothelial cell contraction was investigated. The specific Rho inactivator C3-transferase from Clostridium botulinum as well as microinjection of the isolated Rho-binding domain of Rho kinase or active myosin light chain phosphatase abolished thrombin-stimulated endothelial cell contraction. Conversely, microinjection of constitutively active V14Rho, constitutively active catalytic domain of Rho kinase, or treatment with the phosphatase inhibitor tautomycin caused contraction. These data are consistent with the notion that thrombin activates Rho/Rho kinase to inactivate myosin light chain phosphatase in endothelial cells. In fact, we demonstrate that thrombin transiently inactivated myosin light chain phosphatase, and this correlated with a peak in myosin light chain phosphorylation. C3-transferase abolished the decrease in myosin light chain phosphatase activity as well as the subsequent increase in myosin light chain phosphorylation and cell contraction. These data suggest that thrombin activates the Rho/Rho kinase pathway to inactivate myosin light chain phosphatase as part of a signaling network that controls myosin light chain phosphorylation/contraction in human endothelial cells.
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Cites
Formation of actin stress fibers and focal adhesions enhanced by Rho-kinase
Amano, M., Chihara, K., Kimura, K., Fukata, Y., Nakamura, N., Matsuura, Y., & Kaibuchi, K. (1997) · Science · doi:10.1126/science.275.5304.1308 · Cited by 1,077
Self-citationThe role of integrins in the maintenance of endothelial monolayer integrity.
Lampugnani, M. G., Resnati, M., Dejana, E., & Marchisio, P. C. (1991) · The Journal of cell biology · doi:10.1083/jcb.112.3.479 · Cited by 292
Cited by
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Signaling Mechanisms Regulating Endothelial Permeability
Mehta, D., & Malik, A. B. (2006) · Physiological Reviews · doi:10.1152/physrev.00012.2005 · Cited by 1,720
Somlyo, A. P., & Somlyo, A. V. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-2-00177.x · Cited by 1,207
Regulation of the Cytoskeleton and Cell Adhesion by the Rho Family GTPases in Mammalian Cells
Kaibuchi, K., Kuroda, S., & Amano, M. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.459 · Cited by 1,017
Self-citationCytoskeletal regulation of pulmonary vascular permeability
Dudek, S. M., & Garcia, J. G. N. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.4.1487 · Cited by 985
Metadata
- Authors
- Essler, M., Amano, M., Kruse, H.-J., Kaibuchi, K., Weber, P. C., & Aepfelbacher, M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-08
- Volume
- 273
- Issue
- 34
- Pages
- 21867-21874
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2007513694
- Cited by
- 350
- References
- 2
- FWCI
- 7.99
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Thrombin Inactivates Myosin Light Chain Phosphatase via Rho and Its Target Rho Kinase in Human Endothelial Cells. https://app.cochat.ai/papers/10.1074/jbc.273.34.21867
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- Essler, M., Amano, M., Kruse, H.-J., Kaibuchi, K., Weber, P. C., & Aepfelbacher, M. (1998). Thrombin Inactivates Myosin Light Chain Phosphatase via Rho and Its Target Rho Kinase in Human Endothelial Cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.273.34.21867
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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