A small multigene family encodes Gi signal-transduction proteins (original) (raw)
Abstract
The guanine nucleotide-binding regulatory proteins known as G proteins are receptor-associated signal-transduction molecules that are implicated in the control of a variety of metabolic processes. Recent evidence suggests that G proteins may mediate B-lymphocyte responses to bacterial lipopolysaccharide and may also transduce signals from the T-cell antigen receptor. Since these receptors are uniquely expressed on lymphoid cells, we used molecular cloning strategies to ask whether lymphocytes contain specialized G-protein alpha subunits to assist in signal transduction. Comparison of our two deduced human alpha i amino acid sequences with those previously determined for bovine and rodent G proteins permits the identification of three closely related but distinct types of alpha i molecules that comprise a small multigene family. Using gene-specific probes, we found that both of our alpha i genes are expressed in most cell types but in differing ratios. Our data support the view that a modest repertoire of extremely closely related G proteins mediates the transduction of signals derived from multiple different receptor molecules.
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barrowman M. M., Cockcroft S., Gomperts B. D. Two roles for guanine nucleotides in the stimulus-secretion sequence of neutrophils. Nature. 1986 Feb 6;319(6053):504–507. doi: 10.1038/319504a0. [DOI] [PubMed] [Google Scholar]
- Barth R. K., Kim B. S., Lan N. C., Hunkapiller T., Sobieck N., Winoto A., Gershenfeld H., Okada C., Hansburg D., Weissman I. L. The murine T-cell receptor uses a limited repertoire of expressed V beta gene segments. Nature. 1985 Aug 8;316(6028):517–523. doi: 10.1038/316517a0. [DOI] [PubMed] [Google Scholar]
- Becker E. L., Kermode J. C., Naccache P. H., Yassin R., Munoz J. J., Marsh M. L., Huang C. K., Sha'afi R. I. Pertussis toxin as a probe of neutrophil activation. Fed Proc. 1986 Jun;45(7):2151–2155. [PubMed] [Google Scholar]
- Bray P., Carter A., Simons C., Guo V., Puckett C., Kamholz J., Spiegel A., Nirenberg M. Human cDNA clones for four species of G alpha s signal transduction protein. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8893–8897. doi: 10.1073/pnas.83.23.8893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
- Cockcroft S., Gomperts B. D. Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase. Nature. 1985 Apr 11;314(6011):534–536. doi: 10.1038/314534a0. [DOI] [PubMed] [Google Scholar]
- Didsbury J. R., Ho Y. S., Snyderman R. Human Gi protein alpha-subunit: deduction of amino acid structure from a cloned cDNA. FEBS Lett. 1987 Jan 26;211(2):160–164. doi: 10.1016/0014-5793(87)81428-x. [DOI] [PubMed] [Google Scholar]
- Gilman A. G. G proteins: transducers of receptor-generated signals. Annu Rev Biochem. 1987;56:615–649. doi: 10.1146/annurev.bi.56.070187.003151. [DOI] [PubMed] [Google Scholar]
- Harris B. A., Robishaw J. D., Mumby S. M., Gilman A. G. Molecular cloning of complementary DNA for the alpha subunit of the G protein that stimulates adenylate cyclase. Science. 1985 Sep 20;229(4719):1274–1277. doi: 10.1126/science.3839937. [DOI] [PubMed] [Google Scholar]
- Hescheler J., Rosenthal W., Trautwein W., Schultz G. The GTP-binding protein, Go, regulates neuronal calcium channels. 1987 Jan 29-Feb 4Nature. 325(6103):445–447. doi: 10.1038/325445a0. [DOI] [PubMed] [Google Scholar]
- Hsia J. A., Tsai S. C., Adamik R., Yost D. A., Hewlett E. L., Moss J. Amino acid-specific ADP-ribosylation. Sensitivity to hydroxylamine of [cysteine(ADP-ribose)]protein and [arginine(ADP-ribose)]protein linkages. J Biol Chem. 1985 Dec 25;260(30):16187–16191. [PubMed] [Google Scholar]
- Imboden J. B., Shoback D. M., Pattison G., Stobo J. D. Cholera toxin inhibits the T-cell antigen receptor-mediated increases in inositol trisphosphate and cytoplasmic free calcium. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5673–5677. doi: 10.1073/pnas.83.15.5673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Itoh H., Kozasa T., Nagata S., Nakamura S., Katada T., Ui M., Iwai S., Ohtsuka E., Kawasaki H., Suzuki K. Molecular cloning and sequence determination of cDNAs for alpha subunits of the guanine nucleotide-binding proteins Gs, Gi, and Go from rat brain. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3776–3780. doi: 10.1073/pnas.83.11.3776. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jakway J. P., DeFranco A. L. Pertussis toxin inhibition of B cell and macrophage responses to bacterial lipopolysaccharide. Science. 1986 Nov 7;234(4777):743–746. doi: 10.1126/science.3095921. [DOI] [PubMed] [Google Scholar]
- Katada T., Bokoch G. M., Northup J. K., Ui M., Gilman A. G. The inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. Properties and function of the purified protein. J Biol Chem. 1984 Mar 25;259(6):3568–3577. [PubMed] [Google Scholar]
- Kimura M. Estimation of evolutionary distances between homologous nucleotide sequences. Proc Natl Acad Sci U S A. 1981 Jan;78(1):454–458. doi: 10.1073/pnas.78.1.454. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lerea C. L., Somers D. E., Hurley J. B., Klock I. B., Bunt-Milam A. H. Identification of specific transducin alpha subunits in retinal rod and cone photoreceptors. Science. 1986 Oct 3;234(4772):77–80. doi: 10.1126/science.3529395. [DOI] [PubMed] [Google Scholar]
- Littman D. R., Newton M., Crommie D., Ang S. L., Seidman J. G., Gettner S. N., Weiss A. Characterization of an expressed CD3-associated Ti gamma-chain reveals C gamma domain polymorphism. Nature. 1987 Mar 5;326(6108):85–88. doi: 10.1038/326085a0. [DOI] [PubMed] [Google Scholar]
- Littman D. R., Thomas Y., Maddon P. J., Chess L., Axel R. The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes. Cell. 1985 Feb;40(2):237–246. doi: 10.1016/0092-8674(85)90138-2. [DOI] [PubMed] [Google Scholar]
- Lochrie M. A., Hurley J. B., Simon M. I. Sequence of the alpha subunit of photoreceptor G protein: homologies between transducin, ras, and elongation factors. Science. 1985 Apr 5;228(4695):96–99. doi: 10.1126/science.3856323. [DOI] [PubMed] [Google Scholar]
- Marth J. D., Peet R., Krebs E. G., Perlmutter R. M. A lymphocyte-specific protein-tyrosine kinase gene is rearranged and overexpressed in the murine T cell lymphoma LSTRA. Cell. 1985 Dec;43(2 Pt 1):393–404. doi: 10.1016/0092-8674(85)90169-2. [DOI] [PubMed] [Google Scholar]
- Masters S. B., Stroud R. M., Bourne H. R. Family of G protein alpha chains: amphipathic analysis and predicted structure of functional domains. Protein Eng. 1986 Oct-Nov;1(1):47–54. [PubMed] [Google Scholar]
- Michel T., Winslow J. W., Smith J. A., Seidman J. G., Neer E. J. Molecular cloning and characterization of cDNA encoding the GTP-binding protein alpha i and identification of a related protein, alpha h. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7663–7667. doi: 10.1073/pnas.83.20.7663. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyata T., Yasunaga T., Nishida T. Nucleotide sequence divergence and functional constraint in mRNA evolution. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7328–7332. doi: 10.1073/pnas.77.12.7328. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mustelin T., Pösö H., Andersson L. C. Role of G-proteins in T cell activation: non-hydrolysable GTP analogues induce early ornithine decarboxylase activity in human T lymphocytes. EMBO J. 1986 Dec 1;5(12):3287–3290. doi: 10.1002/j.1460-2075.1986.tb04641.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakamura T., Ui M. Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin. A possible involvement of the toxin-specific substrate in the Ca2+-mobilizing receptor-mediated biosignaling system. J Biol Chem. 1985 Mar 25;260(6):3584–3593. [PubMed] [Google Scholar]
- Northup J. K., Smigel M. D., Sternweis P. C., Gilman A. G. The subunits of the stimulatory regulatory component of adenylate cyclase. Resolution of the activated 45,000-dalton (alpha) subunit. J Biol Chem. 1983 Sep 25;258(18):11369–11376. [PubMed] [Google Scholar]
- Nukada T., Tanabe T., Takahashi H., Noda M., Haga K., Haga T., Ichiyama A., Kanagawa K., Hiranaga M., Matsuo Primary structure of the alpha-subunit of bovine adenylate cyclase-inhibiting G-protein deduced from the cDNA sequence. FEBS Lett. 1986 Mar 3;197(1-2):305–310. doi: 10.1016/0014-5793(86)80347-7. [DOI] [PubMed] [Google Scholar]
- Ponte P., Ng S. Y., Engel J., Gunning P., Kedes L. Evolutionary conservation in the untranslated regions of actin mRNAs: DNA sequence of a human beta-actin cDNA. Nucleic Acids Res. 1984 Feb 10;12(3):1687–1696. doi: 10.1093/nar/12.3.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
- Robishaw J. D., Smigel M. D., Gilman A. G. Molecular basis for two forms of the G protein that stimulates adenylate cyclase. J Biol Chem. 1986 Jul 25;261(21):9587–9590. [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strauss E. C., Kobori J. A., Siu G., Hood L. E. Specific-primer-directed DNA sequencing. Anal Biochem. 1986 Apr;154(1):353–360. doi: 10.1016/0003-2697(86)90536-1. [DOI] [PubMed] [Google Scholar]
- Stryer L., Bourne H. R. G proteins: a family of signal transducers. Annu Rev Cell Biol. 1986;2:391–419. doi: 10.1146/annurev.cb.02.110186.002135. [DOI] [PubMed] [Google Scholar]
- Sullivan K. A., Liao Y. C., Alborzi A., Beiderman B., Chang F. H., Masters S. B., Levinson A. D., Bourne H. R. Inhibitory and stimulatory G proteins of adenylate cyclase: cDNA and amino acid sequences of the alpha chains. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6687–6691. doi: 10.1073/pnas.83.18.6687. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Dop C., Tsubokawa M., Bourne H. R., Ramachandran J. Amino acid sequence of retinal transducin at the site ADP-ribosylated by cholera toxin. J Biol Chem. 1984 Jan 25;259(2):696–698. [PubMed] [Google Scholar]
- West R. E., Jr, Moss J., Vaughan M., Liu T., Liu T. Y. Pertussis toxin-catalyzed ADP-ribosylation of transducin. Cysteine 347 is the ADP-ribose acceptor site. J Biol Chem. 1985 Nov 25;260(27):14428–14430. [PubMed] [Google Scholar]
- Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]