iBet uBet web content aggregator. Adding the entire web to your favor.
iBet uBet web content aggregator. Adding the entire web to your favor.



Link to original content: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC364528
Growth-regulated expression of rhoG, a new member of the ras homolog gene family - PMC Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1992 Jul;12(7):3138–3148. doi: 10.1128/mcb.12.7.3138

Growth-regulated expression of rhoG, a new member of the ras homolog gene family.

S Vincent 1, P Jeanteur 1, P Fort 1
PMCID: PMC364528  PMID: 1620121

Abstract

Cellular transition from the resting state to DNA synthesis involves master switches genes encoding transcriptional factors (e.g., fos, jun, and egr genes), whose targets remain to be fully characterized. To isolate coding sequences specifically accumulated in late G1, a differential screening was performed on a cDNA library prepared from hamster lung fibroblasts stimulated for 5 h with serum. One of the positive clones which displayed a sevenfold induction, turned out to code for a protein sharing homology to Ras-like products. Cloning and sequence analysis of the human homolog revealed that this putative new small GTPase, referred to as rhoG, is more closely related to the rac, CDC42, and TC10 members of the rho (ras homolog) gene family and might have diverged very early during evolution. rhoG mRNA accumulates in proportion to the mitogenic strength of various purified growth factors used for the stimulation, as a consequence of transcriptional activation. G1-specific RNA accumulation is impaired upon addition of antimitogenic cyclic AMP and is enhanced when protein synthesis is inhibited, mainly as a result of RNA stabilization. rhoG mRNA expression is observed in a wide variety of human organs but reaches a particularly high level in lung and placental tissues.

Full text

PDF
3138

Images in this article

Selected References

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

  1. Abo A., Pick E., Hall A., Totty N., Teahan C. G., Segal A. W. Activation of the NADPH oxidase involves the small GTP-binding protein p21rac1. Nature. 1991 Oct 17;353(6345):668–670. doi: 10.1038/353668a0. [DOI] [PubMed] [Google Scholar]
  2. Almendral J. M., Sommer D., Macdonald-Bravo H., Burckhardt J., Perera J., Bravo R. Complexity of the early genetic response to growth factors in mouse fibroblasts. Mol Cell Biol. 1988 May;8(5):2140–2148. doi: 10.1128/mcb.8.5.2140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Avraham H., Weinberg R. A. Characterization and expression of the human rhoH12 gene product. Mol Cell Biol. 1989 May;9(5):2058–2066. doi: 10.1128/mcb.9.5.2058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bacon R. A., Salminen A., Ruohola H., Novick P., Ferro-Novick S. The GTP-binding protein Ypt1 is required for transport in vitro: the Golgi apparatus is defective in ypt1 mutants. J Cell Biol. 1989 Sep;109(3):1015–1022. doi: 10.1083/jcb.109.3.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
  6. Belyavsky A., Vinogradova T., Rajewsky K. PCR-based cDNA library construction: general cDNA libraries at the level of a few cells. Nucleic Acids Res. 1989 Apr 25;17(8):2919–2932. doi: 10.1093/nar/17.8.2919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  8. Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
  9. Bos J. L. The ras gene family and human carcinogenesis. Mutat Res. 1988 May;195(3):255–271. doi: 10.1016/0165-1110(88)90004-8. [DOI] [PubMed] [Google Scholar]
  10. Bourne H. R., Sanders D. A., McCormick F. The GTPase superfamily: a conserved switch for diverse cell functions. Nature. 1990 Nov 8;348(6297):125–132. doi: 10.1038/348125a0. [DOI] [PubMed] [Google Scholar]
  11. Bourne H. R., Sanders D. A., McCormick F. The GTPase superfamily: conserved structure and molecular mechanism. Nature. 1991 Jan 10;349(6305):117–127. doi: 10.1038/349117a0. [DOI] [PubMed] [Google Scholar]
  12. Brawerman G. mRNA decay: finding the right targets. Cell. 1989 Apr 7;57(1):9–10. doi: 10.1016/0092-8674(89)90166-9. [DOI] [PubMed] [Google Scholar]
  13. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  14. Chardin P., Boquet P., Madaule P., Popoff M. R., Rubin E. J., Gill D. M. The mammalian G protein rhoC is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilaments in Vero cells. EMBO J. 1989 Apr;8(4):1087–1092. doi: 10.1002/j.1460-2075.1989.tb03477.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chardin P., Madaule P., Tavitian A. Coding sequence of human rho cDNAs clone 6 and clone 9. Nucleic Acids Res. 1988 Mar 25;16(6):2717–2717. doi: 10.1093/nar/16.6.2717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Chardin P., Tavitian A. The ral gene: a new ras related gene isolated by the use of a synthetic probe. EMBO J. 1986 Sep;5(9):2203–2208. doi: 10.1002/j.1460-2075.1986.tb04485.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ciccarelli C., Philipson L., Sorrentino V. Regulation of expression of growth arrest-specific genes in mouse fibroblasts. Mol Cell Biol. 1990 Apr;10(4):1525–1529. doi: 10.1128/mcb.10.4.1525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Cochran B. H., Reffel A. C., Stiles C. D. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell. 1983 Jul;33(3):939–947. doi: 10.1016/0092-8674(83)90037-5. [DOI] [PubMed] [Google Scholar]
  19. Dessen P., Fondrat C., Valencien C., Mugnier C. BISANCE: a French service for access to biomolecular sequence databases. Comput Appl Biosci. 1990 Oct;6(4):355–356. doi: 10.1093/bioinformatics/6.4.355. [DOI] [PubMed] [Google Scholar]
  20. Didsbury J., Weber R. F., Bokoch G. M., Evans T., Snyderman R. rac, a novel ras-related family of proteins that are botulinum toxin substrates. J Biol Chem. 1989 Oct 5;264(28):16378–16382. [PubMed] [Google Scholar]
  21. Diekmann D., Brill S., Garrett M. D., Totty N., Hsuan J., Monfries C., Hall C., Lim L., Hall A. Bcr encodes a GTPase-activating protein for p21rac. Nature. 1991 May 30;351(6325):400–402. doi: 10.1038/351400a0. [DOI] [PubMed] [Google Scholar]
  22. Drivas G. T., Shih A., Coutavas E., Rush M. G., D'Eustachio P. Characterization of four novel ras-like genes expressed in a human teratocarcinoma cell line. Mol Cell Biol. 1990 Apr;10(4):1793–1798. doi: 10.1128/mcb.10.4.1793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ellis R. W., Defeo D., Shih T. Y., Gonda M. A., Young H. A., Tsuchida N., Lowy D. R., Scolnick E. M. The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes. Nature. 1981 Aug 6;292(5823):506–511. doi: 10.1038/292506a0. [DOI] [PubMed] [Google Scholar]
  24. Evans T., Brown M. L., Fraser E. D., Northup J. K. Purification of the major GTP-binding proteins from human placental membranes. J Biol Chem. 1986 May 25;261(15):7052–7059. [PubMed] [Google Scholar]
  25. Felsenstein J. Evolutionary trees from DNA sequences: a maximum likelihood approach. J Mol Evol. 1981;17(6):368–376. doi: 10.1007/BF01734359. [DOI] [PubMed] [Google Scholar]
  26. Fort P., Rech J., Vie A., Piechaczyk M., Bonnieu A., Jeanteur P., Blanchard J. M. Regulation of c-fos gene expression in hamster fibroblasts: initiation and elongation of transcription and mRNA degradation. Nucleic Acids Res. 1987 Jul 24;15(14):5657–5667. doi: 10.1093/nar/15.14.5657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Frazier W. A. Thrombospondins. Curr Opin Cell Biol. 1991 Oct;3(5):792–799. doi: 10.1016/0955-0674(91)90052-z. [DOI] [PubMed] [Google Scholar]
  28. Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
  29. Hart M. J., Eva A., Evans T., Aaronson S. A., Cerione R. A. Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product. Nature. 1991 Nov 28;354(6351):311–314. doi: 10.1038/354311a0. [DOI] [PubMed] [Google Scholar]
  30. Hein J. Unified approach to alignment and phylogenies. Methods Enzymol. 1990;183:626–645. doi: 10.1016/0076-6879(90)83041-7. [DOI] [PubMed] [Google Scholar]
  31. Herschman H. R. Primary response genes induced by growth factors and tumor promoters. Annu Rev Biochem. 1991;60:281–319. doi: 10.1146/annurev.bi.60.070191.001433. [DOI] [PubMed] [Google Scholar]
  32. Hirschhorn R. R., Aller P., Yuan Z. A., Gibson C. W., Baserga R. Cell-cycle-specific cDNAs from mammalian cells temperature sensitive for growth. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6004–6008. doi: 10.1073/pnas.81.19.6004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Johnson D. I., Pringle J. R. Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity. J Cell Biol. 1990 Jul;111(1):143–152. doi: 10.1083/jcb.111.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Jähner D., Hunter T. The ras-related gene rhoB is an immediate-early gene inducible by v-Fps, epidermal growth factor, and platelet-derived growth factor in rat fibroblasts. Mol Cell Biol. 1991 Jul;11(7):3682–3690. doi: 10.1128/mcb.11.7.3682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kikuchi A., Yamashita T., Kawata M., Yamamoto K., Ikeda K., Tanimoto T., Takai Y. Purification and characterization of a novel GTP-binding protein with a molecular weight of 24,000 from bovine brain membranes. J Biol Chem. 1988 Feb 25;263(6):2897–2904. [PubMed] [Google Scholar]
  36. Lau L. F., Nathans D. Expression of a set of growth-related immediate early genes in BALB/c 3T3 cells: coordinate regulation with c-fos or c-myc. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1182–1186. doi: 10.1073/pnas.84.5.1182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Lau L. F., Nathans D. Identification of a set of genes expressed during the G0/G1 transition of cultured mouse cells. EMBO J. 1985 Dec 1;4(12):3145–3151. doi: 10.1002/j.1460-2075.1985.tb04057.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Leonard D. G., Ziff E. B., Greene L. A. Identification and characterization of mRNAs regulated by nerve growth factor in PC12 cells. Mol Cell Biol. 1987 Sep;7(9):3156–3167. doi: 10.1128/mcb.7.9.3156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lowe D. G., Capon D. J., Delwart E., Sakaguchi A. Y., Naylor S. L., Goeddel D. V. Structure of the human and murine R-ras genes, novel genes closely related to ras proto-oncogenes. Cell. 1987 Jan 16;48(1):137–146. doi: 10.1016/0092-8674(87)90364-3. [DOI] [PubMed] [Google Scholar]
  40. Lu K. H., Levine R. A., Campisi J. c-ras-Ha gene expression is regulated by insulin or insulinlike growth factor and by epidermal growth factor in murine fibroblasts. Mol Cell Biol. 1989 Aug;9(8):3411–3417. doi: 10.1128/mcb.9.8.3411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Madaule P., Axel R. A novel ras-related gene family. Cell. 1985 May;41(1):31–40. doi: 10.1016/0092-8674(85)90058-3. [DOI] [PubMed] [Google Scholar]
  42. Madaule P., Axel R., Myers A. M. Characterization of two members of the rho gene family from the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1987 Feb;84(3):779–783. doi: 10.1073/pnas.84.3.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Magnaldo I., L'Allemain G., Chambard J. C., Moenner M., Barritault D., Pouysségur J. The mitogenic signaling pathway of fibroblast growth factor is not mediated through polyphosphoinositide hydrolysis and protein kinase C activation in hamster fibroblasts. J Biol Chem. 1986 Dec 25;261(36):16916–16922. [PubMed] [Google Scholar]
  44. Magnaldo I., Pouysségur J., Paris S. Thrombin exerts a dual effect on stimulated adenylate cyclase in hamster fibroblasts, an inhibition via a GTP-binding protein and a potentiation via activation of protein kinase C. Biochem J. 1988 Aug 1;253(3):711–719. doi: 10.1042/bj2530711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Magnaldo I., Pouysségur, Paris S. Cyclic AMP inhibits mitogen-induced DNA synthesis in hamster fibroblasts, regardless of the signalling pathway involved. FEBS Lett. 1989 Mar 13;245(1-2):65–69. doi: 10.1016/0014-5793(89)80193-0. [DOI] [PubMed] [Google Scholar]
  46. Majack R. A., Mildbrandt J., Dixit V. M. Induction of thrombospondin messenger RNA levels occurs as an immediate primary response to platelet-derived growth factor. J Biol Chem. 1987 Jun 25;262(18):8821–8825. [PubMed] [Google Scholar]
  47. Munemitsu S., Innis M. A., Clark R., McCormick F., Ullrich A., Polakis P. Molecular cloning and expression of a G25K cDNA, the human homolog of the yeast cell cycle gene CDC42. Mol Cell Biol. 1990 Nov;10(11):5977–5982. doi: 10.1128/mcb.10.11.5977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Nikaido T., Bradley D. W., Pardee A. B. Molecular cloning of transcripts that accumulate during the late G1 phase in cultured mouse cells. Exp Cell Res. 1991 Jan;192(1):102–109. doi: 10.1016/0014-4827(91)90163-o. [DOI] [PubMed] [Google Scholar]
  49. Olofsson B., Chardin P., Touchot N., Zahraoui A., Tavitian A. Expression of the ras-related ralA, rho12 and rab genes in adult mouse tissues. Oncogene. 1988 Aug;3(2):231–234. [PubMed] [Google Scholar]
  50. Paterson H. F., Self A. J., Garrett M. D., Just I., Aktories K., Hall A. Microinjection of recombinant p21rho induces rapid changes in cell morphology. J Cell Biol. 1990 Sep;111(3):1001–1007. doi: 10.1083/jcb.111.3.1001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Piechaczyk M., Blanchard J. M., Marty L., Dani C., Panabieres F., El Sabouty S., Fort P., Jeanteur P. Post-transcriptional regulation of glyceraldehyde-3-phosphate-dehydrogenase gene expression in rat tissues. Nucleic Acids Res. 1984 Sep 25;12(18):6951–6963. doi: 10.1093/nar/12.18.6951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Pizon V., Chardin P., Lerosey I., Olofsson B., Tavitian A. Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the 'effector' region. Oncogene. 1988 Aug;3(2):201–204. [PubMed] [Google Scholar]
  53. Polakis P. G., Weber R. F., Nevins B., Didsbury J. R., Evans T., Snyderman R. Identification of the ral and rac1 gene products, low molecular mass GTP-binding proteins from human platelets. J Biol Chem. 1989 Oct 5;264(28):16383–16389. [PubMed] [Google Scholar]
  54. Reibel L., Dorseuil O., Stancou R., Bertoglio J., Gacon G. A hemopoietic specific gene encoding a small GTP binding protein is overexpressed during T cell activation. Biochem Biophys Res Commun. 1991 Mar 15;175(2):451–458. doi: 10.1016/0006-291x(91)91585-z. [DOI] [PubMed] [Google Scholar]
  55. Rüther U., Wagner E. F., Müller R. Analysis of the differentiation-promoting potential of inducible c-fos genes introduced into embryonal carcinoma cells. EMBO J. 1985 Jul;4(7):1775–1781. doi: 10.1002/j.1460-2075.1985.tb03850.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Santos E., Nebreda A. R. Structural and functional properties of ras proteins. FASEB J. 1989 Aug;3(10):2151–2163. doi: 10.1096/fasebj.3.10.2666231. [DOI] [PubMed] [Google Scholar]
  57. Schneider C., King R. M., Philipson L. Genes specifically expressed at growth arrest of mammalian cells. Cell. 1988 Sep 9;54(6):787–793. doi: 10.1016/s0092-8674(88)91065-3. [DOI] [PubMed] [Google Scholar]
  58. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  59. Shinjo K., Koland J. G., Hart M. J., Narasimhan V., Johnson D. I., Evans T., Cerione R. A. Molecular cloning of the gene for the human placental GTP-binding protein Gp (G25K): identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9853–9857. doi: 10.1073/pnas.87.24.9853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Touchot N., Chardin P., Tavitian A. Four additional members of the ras gene superfamily isolated by an oligonucleotide strategy: molecular cloning of YPT-related cDNAs from a rat brain library. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8210–8214. doi: 10.1073/pnas.84.23.8210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Valencia A., Chardin P., Wittinghofer A., Sander C. The ras protein family: evolutionary tree and role of conserved amino acids. Biochemistry. 1991 May 14;30(19):4637–4648. doi: 10.1021/bi00233a001. [DOI] [PubMed] [Google Scholar]
  62. Van Der Sluijs P., Hull M., Zahraoui A., Tavitian A., Goud B., Mellman I. The small GTP-binding protein rab4 is associated with early endosomes. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6313–6317. doi: 10.1073/pnas.88.14.6313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Van Obberghen-Schilling E., Chambard J. C., Paris S., L'Allemain G., Pouysségur J. alpha-Thrombin-induced early mitogenic signalling events and G0 to S-phase transition of fibroblasts require continual external stimulation. EMBO J. 1985 Nov;4(11):2927–2932. doi: 10.1002/j.1460-2075.1985.tb04025.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Vincent S., Fort P. Nucleotide sequence of hamster glyceraldehyde-3-phosphate dehydrogenase mRNA. Nucleic Acids Res. 1990 May 25;18(10):3054–3054. doi: 10.1093/nar/18.10.3054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Wilson T., Treisman R. Removal of poly(A) and consequent degradation of c-fos mRNA facilitated by 3' AU-rich sequences. Nature. 1988 Nov 24;336(6197):396–399. doi: 10.1038/336396a0. [DOI] [PubMed] [Google Scholar]
  66. Yarden Y., Ullrich A. Growth factor receptor tyrosine kinases. Annu Rev Biochem. 1988;57:443–478. doi: 10.1146/annurev.bi.57.070188.002303. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES