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Several regulators of G protein signaling (RGS) proteins contain a G protein [Gamma]-subunit-like (GGL) domain, which, as we have shown, binds to [G.sub.[Beta]5] subunits. Here, we extend our original findings by describing another GGL-domain-containing RGS, human RGS6. When RGS6 is coexpressed with different [G.sub.[Beta]] subunits, only RGS6 and [G.sub.[Beta]5] interact. The expression of mRNA for RGS6 and [G.sub.[Beta]5] in human tissues overlaps. Predictions of [Alpha]-helical and coiled-coil character within GGL domains, coupled with measurements of [G.sub.[Beta]] binding by GGL domain mutants, support the contention that [G.sub.[Gamma]]-like regions within RGS proteins interact with [G.sub.[Beta]5] subunits in a fashion comparable to conventional [G.sub.[Beta]]/[G.sub.[Gamma]] pairings. Mutation of the highly conserved Phe-61 residue of [G.sub.[Gamma]2] to tryptophan, the residue present in all GGL domains, increases the stability of the [G.sub.[Beta]5]/[G.sub.[Gamma]2] heterodimer, highlighting the importance of this residue to GGL/[G.sub.[Beta]5] association.

Mitochondria are important in the control of cell death, or apoptosis.An apoptosis-inducing factor (AIF), able to induce apoptosis of isolated nuclei, has been identified and cloned. The AIF flavoprotein can translocated to the nucleus when apoptosis is induced. Recombinant AIF leads to chromatin condensation and large scale DNA fragmentation. Purified mitochondria are induced to release cytochrome c and caspase-9. The wide-ranging caspase inhibitor Z-VAD.fmk. does not prevent any of those effects.

Regulators of G protein signaling (RGS) proteins act as GTPase-activating proteins (GAPs) toward the [Alpha] subunits of heterotrimeric, signal-transducing G proteins. RGS11 contains a G protein [Gamma], subunit-like (GGL) domain between its Dishevelled/Egl-10/Pleckstrin and RGS domains. GGL domains are also found in RGS6, RGS7, RGS9, and the Caenorhabditis elegans protein EGL-10. Coexpression of RGS11 with different [G.sub.[Beta]] subunits reveals specific interaction between RGS11 and [G.sub.[Beta]5]. The expression of mRNA for RGS11 and [G.sub.[Beta]5] in human tissues overlaps. The [G.sub.[Beta]5]/RGS11 heterodimer acts as a GAP on [G.sub.[Alpha]0], apparently selectively. RGS proteins that contain GGL domains appear to act as GAPs for [G.sub.[Alpha]] proteins and form complexes with specific [G.sub.[Beta]] subunits, adding to the combinatorial complexity of G protein-mediated signaling pathways.