Connell, L. E., Helfman, D. M. (June 2006) Myosin light chain kinase plays a role in the regulation of epithelial cell survival. J Cell Sci, 119 (Pt 11). pp. 2269-81. ISSN 0021-9533 (Print)
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Abstract
Myosin II activation is essential for stress fiber and focal adhesion formation, and is implicated in integrin-mediated signaling events. In this study we investigated the role of acto-myosin contractility, and its main regulators, i.e. myosin light chain kinase (MLCK) and Rho-kinase (ROCK) in cell survival in normal and Ras-transformed MCF-10A epithelial cells. Treatment of cells with pharmacological inhibitors of MLCK (ML-7 and ML-9), or expression of dominant-negative MLCK, led to apoptosis in normal and transformed MCF-10A cells. By contrast, treatment of cells with a ROCK inhibitor (Y-27632) did not induce apoptosis in these cells. Apoptosis following inhibition of myosin II activation by MLCK is probably meditated through the death receptor pathway because expression of dominant-negative FADD blocked apoptosis. The apoptosis observed after MLCK inhibition is rescued by pre-treatment of cells with integrin-activating antibodies. In addition, this rescue of apoptosis is dependent on FAK activity, suggesting the participation of an integrin-dependent signaling pathway. These studies demonstrate a newly discovered role for MLCK in the generation of pro-survival signals in both untransformed and transformed epithelial cells and supports previous work suggesting distinct cellular roles for Rho-kinase- and MLCK-dependent regulation of myosin II.
| Item Type: | Paper |
|---|---|
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > integrin bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > myosin |
| CSHL Authors: | |
| Depositing User: | CSHL Librarian |
| Date: | 1 June 2006 |
| Date Deposited: | 19 Dec 2011 19:05 |
| Last Modified: | 06 Nov 2017 20:05 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/22776 |
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