Constitutively Active Gαq and Gα13 Trigger Apoptosis through Different Pathways*

We investigated the effect of expression of constitutively active Gα mutants on cell survival. Transfection of constitutively active Gαq and Gα13 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 Gα-subunits, the signaling pathways involved in this cellular function were investigated. Whereas Gαq induced apoptosis via a protein kinaseC-dependent pathway, Gα13 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 Gαq and Gα13 triggered apoptosis in high serum as well as in defined medium.

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