G protein diversity: a distinct class of α 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 alpha 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 alpha subunits, G alpha q and G alpha 11, 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 alpha subunits. Multiple mRNAs as large as 7.5 kilobases hybridize to G alpha q specific probes and are expressed at various levels in many different tissues. G alpha 11 is encoded by a single 4.0-kilobase message which is expressed ubiquitously. Amino acid sequence comparisons suggest that G alpha q and G alpha 11 represent a third class of alpha subunits. A member of this class was found in Drosophila melanogaster. This alpha subunit, DG alpha q, is 76% identical to G alpha q. The presence of the Gq class in both vertebrates and invertebrates points to a role that is central to signal transduction in multicellular organisms. We suggest that these alpha subunits may be involved in pertussis toxin-insensitive pathways coupled to phospholipase C.
Additional InformationCopyright © 1990 by the National Academy of Sciences. Contributed by Melvin I. Simon, August 21, 1990. We thank Paul Sternweiss and David Hyde for communicating their results prior to publication. We are grateful to Tom Wilkie for help with the PCR analysis of mRNA, Bruce Hamilton and Mike Palazzolo for Drosophila RNA and cDNA libraries, Don Seto and Carol Lee for sequencing assistance, and T. Wilkie and Narasimhan Gautam for reading the manuscript. This work was supported by Grant GM34236 from the National Institutes of Health. The sequences reported in this paper have been deposited in the GenBank data base (accession nos. M55412 for Gαq and M55411 for Gα11. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Published - STRApnas90.pdf