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The human papillomavirus type 16 E5 protein modulates phospholipase C-γ-1 activity and phosphatidyl inositol turnover in mouse fibroblasts

Oncogene volume 18, pages 6714–6718 (1999)Cite this article

Abstract

The human papillomavirus type 16 E5 (HPV16-E5) protein is a membrane protein that has been associated with malignant growth. The protein affects growth factor-mediated signal transduction in a ligand-dependent manner. We show now that E5 expression in A31 fibroblasts results in an increased level of diacylglycerol (DAG) and inositol phosphates. Immunoprecipitation of phospholipase C-γ-1 (PLC-γ-1) with specific antibodies and immunoblotting with anti-phosphotyrosine antibodies reveal a large increase in tyrosine phosphorylation of the enzyme in E5-expressing cells compared to control vector-transfected cells. This activation of tyrosine phosphorylation is growth factor independent. In addition, an enhanced formation of phosphatidic acid (PA) was observed in E5 cells. This increase did not result from activation of phospholipase D (PLD), although the enzyme was activatable by treatment with phorbol ester. Thus, a phosphohydrolase-mediated DAG synthesis from PLD-produced PA can be excluded. The observed effects were not further enhanced by EGF showing that the presence of the growth factor is not necessary for maintaining permanent activation of PLC-γ-1 in E5-expressing cells. The DAG- and inositol phosphate-mediated signal cascade within the cells is thus effectively uncoupled from external control via EGF and its receptor in the presence of E5 protein.

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References

  • Auvinen E, Crusius K, Steuer B and Alonso A. . 1997 Int. J. Cancer. 11: 1297–1304.

  • Bligh EG and Dyer WJ. . 1959 Can. J. Biochem. Physiol. 37: 911–918.

  • Bouvard V, Matlashewski G, Gu ZM, Storey A and Banks L. . 1994 Virology 203: 73–80.

  • Conrad M, Bubb VJ and Schlegel R. . 1993 J. Virol. 67: 6170–6178.

  • Crusius K, Auvinen E and Alonso A. . 1997 Oncogene 15: 1437–1444.

  • Crusius K, Auvinen E, Steuer B, Gaissert H and Alonso A. . 1998 Exp. Cell Res. 241: 76–83.

  • Divecha N and Irvine RF. . 1995 Cell 80: 269–278.

  • Exton JH. . 1998 Biochim. Biophys. Acta. 1436: 105–115.

  • Faccini AM, Cairney M, Ashrafi GJ, Finbow ME, Campo MS and Pitts D. . 1996 J. Virol. 70: 9041–9045.

  • Faulkner-Valle G and Banks L. . 1995 J. Gen. Virol. 76: 1239–1245.

  • Hokin LE. . 1985 Ann. Rev. Biochem. 54: 205–235.

  • Homma MK, Homma Y, Yamasaki M, Ohmi-Imajoh S and Yuasa Y. . 1996 Cell Growth Diff. 7: 281–288.

  • Kaszkin M, Seidler L, Kast R and Kinzel V. . 1992 Biochem. J. 287: 51–57.

  • Kaszkin M, Richards J and Kinzel V. . 1996 Biochem. J. 314: 129–138.

  • Katan M. . 1996 Cancer Surv. 27: 199–211.

  • Khare S, Bolt MJ, Wali RK, Skarosi SR, Roy HK, Niedziela S, Scaglioni-Sewell B, Aquino B, Abraham C, Sitrin MD, Brasitus TA and Bissonnette M. . 1997 J. Clin. Invest. 99: 1831–1841.

  • Kiss Z, Crilly KS and Anderson WH. . 1998 Biochim. Biophys. Acta. 1392: 109–118.

  • Kobayashi N and Kanfer JN. . 1987 J. Neurochem. 48: 1597–1603.

  • Lambeth JD and Ryu SH. . 1996 Glycerolipids in signal transduction. In: Biochemistry of Lipids, lipoproteins and membranes. Vance DE and Vance JE. (eds).. Elsevier: Amsterdam. pp. 237–225.

    Book  Google Scholar 

  • Leechanachai P, Banks L, Moreau F and Matlashewski G. . 1992 Oncogene 7: 19–25.

  • Liscovitch M. . 1996 J. Lipid Mediat. Cell Signal. 14: 215–221.

  • Leptak C, Ramón y Cajal S, Kulke R, Horwitz BH, Riese II DJ, Dotto GP and DiMaio D. . 1991 J. Virol. 65: 7078–7083.

  • Nishizuka Y. . 1992 Science 258: 607–614.

  • Oelze I, Kartenbeck J, Crusius K and Alonso A. . 1995 J. Virol. 69: 4489–4494.

  • Pim WD, Collins M and Banks L. . 1992 Oncogene 7: 27–32.

  • Rahimi N, Tremblay E, McAdam L, Park M, Schwall R and Elliot B. . 1996 Cell Growth Differ. 7: 263–270.

  • Reynolds NJ, Talwar HS, Baldassare JJ, Henderson PA, Elder JT, Voorhees JJ and Fischer GJ. . 1993 Biochem. J. 294: 535–544.

  • Sakane F and Kanoh H. . 1997 Int. J. Biochem. Cell. Biol. 29: 1139–1143.

  • Schmidt M, Voss M, Thiel M, Bauer B, Grannass A, Tapp E, Cool RH, de Günzburg J, von Eichel Streiber C and Jacobs KH. . 1998 J. Biol. Chem. 273: 7413–7422.

  • Singer WD, Brown HL and Sternweis PC. . 1997 Annu. Rev. Bioche. 66: 475–509.

  • Straight SW, Hinkle PM, Jewers RJ and McCance DJ. . 1993 J. Virol. 67: 4521–4532.

  • Wagner H, Lissau A, Holzi J and Horammer L. . 1962 J. Lipid Res. 3: 177–180.

  • Wahl M and Carpenter G. . 1988 J. Biol. Chem. 263: 7581–7590.

  • Yeo EJ and Exton JH. . 1995 J. Biol. Chem. 270: 3980–3988.

  • zur Hausen H. . 1989 Cancer Res. 49: 4677–4681.

  • zur Hausen H. . 1991 Virology 184: 9–13.

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  1. Deutsches Krebsforschungszentrum, Im Neuenheimer Feld-242, 69120, Heidelberg, Germany

    Kerstin Crusius, Marietta Kaszkin, Volker Kinzel & Angel Alonso

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  1. Kerstin Crusius
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Crusius, K., Kaszkin, M., Kinzel, V. et al. The human papillomavirus type 16 E5 protein modulates phospholipase C-γ-1 activity and phosphatidyl inositol turnover in mouse fibroblasts. Oncogene 18, 6714–6718 (1999). https://doi.org/10.1038/sj.onc.1203075

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