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. 1989 Dec;9(12):5434–5439. doi: 10.1128/mcb.9.12.5434

The G protein alpha o subunit alters morphology, growth kinetics, and phospholipid metabolism of somatic cells.

D B Bloch 1, J V Bonventre 1, E J Neer 1, J G Seidman 1
PMCID: PMC363711  PMID: 2511433

Abstract

The physiological role of the alpha o subunit of guanine nucleotide-binding (G) protein was investigated with a murine adrenal cell line (Y1) transfected with a rat alpha o cDNA cloned in a retroviral expression vector. The parental cell line lacked detectable alpha o subunit. Expression of the alpha o cDNA in transfected cell lines was confirmed by Western blot (immunoblot) analysis. The rat alpha o subunit interacted with murine beta and gamma subunits and associated with cell membranes. Y1 cells containing large amounts of alpha o subunit had altered cellular morphology and reduced rate of cell division. In addition, GTP-gamma S-stimulated release of arachidonic acid from these cells was significantly increased compared with that in control cells. The alpha o subunit appears directly or indirectly to regulate cellular proliferation, morphology, and phospholipid metabolism.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Axelrod J., Burch R. M., Jelsema C. L. Receptor-mediated activation of phospholipase A2 via GTP-binding proteins: arachidonic acid and its metabolites as second messengers. Trends Neurosci. 1988 Mar;11(3):117–123. doi: 10.1016/0166-2236(88)90157-9. [DOI] [PubMed] [Google Scholar]
  2. Bonventre J. V., Swidler M. Calcium dependency of prostaglandin E2 production in rat glomerular mesangial cells. Evidence that protein kinase C modulates the Ca2+-dependent activation of phospholipase A2. J Clin Invest. 1988 Jul;82(1):168–176. doi: 10.1172/JCI113566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burch R. M., Axelrod J. Dissociation of bradykinin-induced prostaglandin formation from phosphatidylinositol turnover in Swiss 3T3 fibroblasts: evidence for G protein regulation of phospholipase A2. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6374–6378. doi: 10.1073/pnas.84.18.6374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Collu R., Bouvier C., Lagacé G., Unson C. G., Milligan G., Goldsmith P., Spiegel A. M. Selective deficiency of guanine nucleotide-binding protein Go in two dopamine-resistant pituitary tumors. Endocrinology. 1988 Mar;122(3):1176–1178. doi: 10.1210/endo-122-3-1176. [DOI] [PubMed] [Google Scholar]
  5. Conklin B. R., Brann M. R., Buckley N. J., Ma A. L., Bonner T. I., Axelrod J. Stimulation of arachidonic acid release and inhibition of mitogenesis by cloned genes for muscarinic receptor subtypes stably expressed in A9 L cells. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8698–8702. doi: 10.1073/pnas.85.22.8698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Goldsmith P., Backlund P. S., Jr, Rossiter K., Carter A., Milligan G., Unson C. G., Spiegel A. Purification of heterotrimeric GTP-binding proteins from brain: identification of a novel form of Go. Biochemistry. 1988 Sep 6;27(18):7085–7090. doi: 10.1021/bi00418a062. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Huff R. M., Axton J. M., Neer E. J. Physical and immunological characterization of a guanine nucleotide-binding protein purified from bovine cerebral cortex. J Biol Chem. 1985 Sep 5;260(19):10864–10871. [PubMed] [Google Scholar]
  10. Jones D. T., Reed R. R. Molecular cloning of five GTP-binding protein cDNA species from rat olfactory neuroepithelium. J Biol Chem. 1987 Oct 15;262(29):14241–14249. [PubMed] [Google Scholar]
  11. Kim D., Lewis D. L., Graziadei L., Neer E. J., Bar-Sagi D., Clapham D. E. G-protein beta gamma-subunits activate the cardiac muscarinic K+-channel via phospholipase A2. Nature. 1989 Feb 9;337(6207):557–560. doi: 10.1038/337557a0. [DOI] [PubMed] [Google Scholar]
  12. Kitayama H., Sugimoto Y., Matsuzaki T., Ikawa Y., Noda M. A ras-related gene with transformation suppressor activity. Cell. 1989 Jan 13;56(1):77–84. doi: 10.1016/0092-8674(89)90985-9. [DOI] [PubMed] [Google Scholar]
  13. Kumagai A., Pupillo M., Gundersen R., Miake-Lye R., Devreotes P. N., Firtel R. A. Regulation and function of G alpha protein subunits in Dictyostelium. Cell. 1989 Apr 21;57(2):265–275. doi: 10.1016/0092-8674(89)90964-1. [DOI] [PubMed] [Google Scholar]
  14. Kurachi Y., Ito H., Sugimoto T., Shimizu T., Miki I., Ui M. Arachidonic acid metabolites as intracellular modulators of the G protein-gated cardiac K+ channel. Nature. 1989 Feb 9;337(6207):555–557. doi: 10.1038/337555a0. [DOI] [PubMed] [Google Scholar]
  15. Lochrie M. A., Simon M. I. G protein multiplicity in eukaryotic signal transduction systems. Biochemistry. 1988 Jul 12;27(14):4957–4965. doi: 10.1021/bi00414a001. [DOI] [PubMed] [Google Scholar]
  16. Masters S. B., Sullivan K. A., Miller R. T., Beiderman B., Lopez N. G., Ramachandran J., Bourne H. R. Carboxyl terminal domain of Gs alpha specifies coupling of receptors to stimulation of adenylyl cyclase. Science. 1988 Jul 22;241(4864):448–451. doi: 10.1126/science.2899356. [DOI] [PubMed] [Google Scholar]
  17. Murayama T., Ui M. Possible involvement of a GTP-binding protein, the substrate of islet-activating protein, in receptor-mediated signaling responsible for cell proliferation. J Biol Chem. 1987 Sep 15;262(26):12463–12467. [PubMed] [Google Scholar]
  18. Neer E. J., Clapham D. E. Roles of G protein subunits in transmembrane signalling. Nature. 1988 May 12;333(6169):129–134. doi: 10.1038/333129a0. [DOI] [PubMed] [Google Scholar]
  19. Neer E. J., Lok J. M., Wolf L. G. Purification and properties of the inhibitory guanine nucleotide regulatory unit of brain adenylate cyclase. J Biol Chem. 1984 Nov 25;259(22):14222–14229. [PubMed] [Google Scholar]
  20. Nukada T., Mishina M., Numa S. Functional expression of cloned cDNA encoding the alpha-subunit of adenylate cyclase-stimulating G-protein. FEBS Lett. 1987 Jan 19;211(1):5–9. doi: 10.1016/0014-5793(87)81263-2. [DOI] [PubMed] [Google Scholar]
  21. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  22. Postlethwaite A. E., Jackson B. K., Beachey E. H., Kang A. H. Formation of multinucleated giant cells from human monocyte precursors. Mediation by a soluble protein from antigen-and mitogen-stimulated lymphocytes. J Exp Med. 1982 Jan 1;155(1):168–178. doi: 10.1084/jem.155.1.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Price J., Turner D., Cepko C. Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer. Proc Natl Acad Sci U S A. 1987 Jan;84(1):156–160. doi: 10.1073/pnas.84.1.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. VanDongen A. M., Codina J., Olate J., Mattera R., Joho R., Birnbaumer L., Brown A. M. Newly identified brain potassium channels gated by the guanine nucleotide binding protein Go. Science. 1988 Dec 9;242(4884):1433–1437. doi: 10.1126/science.3144040. [DOI] [PubMed] [Google Scholar]
  25. Wigler M., Pellicer A., Silverstein S., Axel R. Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor. Cell. 1978 Jul;14(3):725–731. doi: 10.1016/0092-8674(78)90254-4. [DOI] [PubMed] [Google Scholar]

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