Althoefer, Henning and Eversole-Cire, Pamela and Simon, Melvin I. (1997) Constitutively Active Galpha q and Galpha 13 Trigger Apoptosis through Different Pathways. Journal of Biological Chemistry, 1997 (39). pp. 24380-24386. ISSN 0021-9258. http://resolver.caltech.edu/CaltechAUTHORS:ALTjbc97
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We investigated the effect of expression of constitutively active Galpha mutants on cell survival. Transfection of constitutively active Galphaq and Galpha13 in two different cell lines caused condensation of genomic DNA and nuclear fragmentation. Endonuclease cleavage of genomic DNA was followed by labeling the DNA fragments and subsequent flow cytometric analysis. The observed cellular phenotype was identical to the phenotype displayed by cells undergoing apoptosis. To distinguish between the apoptosis-inducing ability of the two Galpha-subunits, the signaling pathways involved in this cellular function were investigated. Whereas Galpha q induced apoptosis via a protein kinaseC-dependent pathway, Galpha13 caused programmed cell death through a pathway involving the activation of the small G-protein Rho. Both of the pathways leading to apoptosis were blocked by overexpression of bcl-2. In contrast to other apoptosis-inducing systems, expression of constitutively active Galphaq and Galpha13 triggered apoptosis in high serum as well as in defined medium.
|Additional Information:||©1997 by The American Society for Biochemistry and Molecular Biology, Inc. (Received for publication, February 24, 1997, and in revised form, June 23, 1997) We thank Dr. J. Heller Brown for the gift of the RasN17 expression plasmid. We also thank S. Diamond for professional help with flow cytometric analysis and Dr. T. Wieland for helpful discussion. CHO cells were generously provided by Dr. M. C. Jasek. This work was supported by National Institutes of Health Grant GM 34236. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.|
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|Deposited On:||14 Dec 2006|
|Last Modified:||26 Dec 2012 09:23|
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