Affiliation:
1. Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA, 92037, USA
Abstract
Programmed cell death is crucial for the development and maintenance of multicellular organisms. The decision to live, or to die, depends, at the cellular level, upon the cell's interaction with extracellular cues that trigger cell signaling pathways promoting survival or death. The extracellular matrix (ECM) influences the execution of the apoptotic program through the actions of adhesion receptors. Among these, integrins initiate a variety of downstream signaling events in response to ECM ligation. Integrins directly activate survival pathways via the PI 3-kinase and MAPK pathways and act as essential cofactors for their stimulation by growth factors. Conversely,elevated integrin expression in the absence of appropriate ligands, or in the presence of natural or synthetic antagonists, can promote apoptosis under otherwise permissive growth conditions. Integrins thus act in a crucial biosensory role, coordinating survival or death responses as a function of ECM composition. This dual function provides an elegant mechanism through which tissue-remodeling events may regulate cell death or survival in a temporal,ECM-governed manner.
Publisher
The Company of Biologists
Reference140 articles.
1. Abreu, M. T., Arnold, E. T., Chow, J. Y. and Barrett, K. E.(2001). Phosphatidylinsitol 3-kinase-dependent pathways oppose Fas-induced apoptosis and limit chloride secretion in human intestinal epithelial cells. Implications for inflammatory diarrheal states.J. Biol. Chem.276, 47563-47574.
2. Algeciras-Schimnich, A., Shen, L., Barnhart, B. C., Murmann, A. E., Burkhardt, J. K. and Peter, M. E. (2002). Molecular ordering of the initial signaling events of CD95. Mol. Cell. Biol.22, 207-220.
3. Almeida, E. A., Ilic, D., Han, Q., Hauck, C. R., Jin, F.,Kawakatsu, H., Schlaepfer, D. D. and Damsky, C. H. (2000). Matrix survival signaling: from fibronectin via focal adhesion kinase to c-Jun NH(2)-terminal kinase. J. Cell Biol.149, 741-754.
4. Aoki, K., Kurooka, M., Chen, J. J., Petryniak, J., Nabel, E. G. and Nabel, G. J. (2001). Extracellular matrix interacts with soluble CD95L: retention and enhancement of cytotoxicity. Nat. Immunol.2, 333-337.
5. Aoudjit, F. and Vuori, K. (2000). Engagement of the alpha2betal integrin inhibits Fas ligand expression and activation-induced cell death in T cells in a focal adhesion kinase-dependent manner.Blood95, 2044-2051.
Cited by
504 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献