G-PROTEIN DIVERSITY - A DISTINCT CLASS OF ALPHA-SUBUNITS IS PRESENT IN VERTEBRATES AND INVERTEBRATES

Heterotrimeric guanine nucleotide-binding proteins (G proteins) are integral to the signal transduction pathways that mediate the cell's response to many hormones, neuromodulators, and a variety of other ligands. While many signaling processes are guanine nucleotide dependent, the precise coupling between a variety of receptors, G proteins, and effectors remains obscure. We found that the family of genes that encode the α subunits of heterotrimeric G proteins is much larger than had previously been supposed. These novel alpha subunits could account for some of the diverse activities attributed to G proteins. We have now obtained cDNA clones encoding two murine α subunits, Gα(q) and Gα11, that are 88% identical. They lack the site that is ordinarily modified by pertussis toxin and their sequences vary from the canonical Gly-Ala-Gly-Glu-Ser (GAGES) amino acid sequence found in most other G protein α subunits. Multiple mRNAs as large as 7.5 kilobases hybridize to Gα(q) specific probes and are expressed at various levels in many different tissues. Gα11 is encoded by a single 4.0-kilobase message which is expressed ubiquitously. Amino acid sequence comparisons suggest that Gα(q) and Gα11 represent a third class of α subunits. A member of this class was found in Drosophila melanogaster. This α subunit, DGα(q), is 76% identical to Gα(q). The presence of the G(q) class in both vertebrates and invertebrates points to a role that is central to signal transduction in multicellular organisms. We suggest that these α subunits may be involved in pertussis toxin-insensitive pathways coupled to phospholipase C.