Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

p95vav associates with the type I interferon (IFN) receptor and contributes to the antiproliferative effect of IFN-α in megakaryocytic cell lines

Oncogene volume 19, pages 387–394 (2000)Cite this article

Abstract

The vav proto-oncogene product is a 95 kDa protein predominantly expressed in hematopoietic cells. Vav presents a wide range of functional domains, including structural domains known to be involved in signal transduction. Triggering of various cytokine receptors among which type I interferon receptor induces a rapid and transient tyrosine phosphorylation of p95vav. Nevertheless, the biological functions of p95vav are still unclear. This report is the first documentation on the physical association of p95vav with both α and β type I interferon receptor chains, as demonstrated by co-immunoprecipitation and Western blot analysis in megakaryocytic cells (Dami and UT7). This interaction is increased by interferon-α/β stimulation. Moreover, p95vav phosphorylated subsequently to type I interferon treatment, is translocated in the nucleus; a concomitant increase of its association with the regulatory subunit of the nuclear DNA-dependent protein kinase, KU-70 is observed in the nucleus. To determine whether p95vav participates in the biological response to type I interferons, we studied the effects of non modified Vav oligodeoxynucleotides on the antiproliferative effect of interferon-α on megakaryocytic cells. By this oligodeoxynucleotide strategy, we show that p95vav contributes greatly to the cell proliferation inhibition induced by type I IFN.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

Abbreviations

IFN:

Interferon

IFNAR:

Interferon Alpha Receptor

GM-CSF:

Granulocyte Macrophage Colony-Stimulating Factor

Stats:

Signal transducers and activators proteins

ISGF3:

Interferon-Stimulated Gene Factor 3

CML:

Chronic Myelogenous Leukemia

CMPDs:

Chronic Myeloproliferative Disorders

Epo:

Erythropoietin

References

  • Adams JM, Houston H, Allen J, Lints T and Harvey R. . 1992 Oncogene 7: 611–618.

  • Alai M, Mui AL, Culter RL, Bustelo XR, Barbacid M and Krystal G. . 1992 J. Biol. Chem. 267: 18021–18025.

  • Bustelo XR and Barbacid M. . 1992 Science 256: 1196–1199.

  • Bustelo XR, Rubin SD, Suen KL, Carrasco D and Barbacid M. . 1993 Cell Growth Differ. 4: 297–308.

  • Carlo-Stella C, Cazzola M, Gasner A, Barosi G, Dezza L, Meloni F, Pedrazzoli P, Hoelzer D and Ascari E. . 1987 Blood 70: 1014–1019.

  • Clevenger CV, Ngo W, Sokol DL, Luger SM and Gewirtz AM. . 1995 J. Biol. Chem. 270: 13246–13253.

  • Cohen B, Novick D, Barak S and Rubinstein M. . 1995 Mol. Cell. Biol. 15: 4208–4214.

  • Colamonici OR, Domanski P, Krolewski JJ, Fu NY, Pfeffer LM, Sweet ME and Platanias LC. . 1994 J. Biol. Chem. 269: 5660–5666.

  • Croze E, Russell-Harde D, Wagner TC, Pu H, Pfeffer LM and Perez HD. . 1996 J. Biol. Chem. 271: 33165–33168.

  • Darnell JE Jr, Kerr IM and Stark GR. . 1994 Science 264: 1415–1421.

  • Domanski P, Witte M, Kellum M, Rubinstein M, Hackett R, Pitha P and Colamonici OR. . 1995 J. Biol. Chem. 270: 21606–21611.

  • Domanski P, Nadeau OW, Platanias LC, Fish E, Kellum M, Pitha P and Colamonici OR. . 1998 J. Biol. Chem. 273: 3144–3147.

  • Einat M, Resnitzky D and Kimchi A. . 1985 Nature 313: 597–600.

  • Evans GA, Howard OM, Erwin R and Farrar WL. . 1993 Biochem. J. 294: 339–342.

  • Greenberg SM, Rosenthal DS, Greeley TA, Tantravahi R and Hardin RI. . 1988 Blood 72: 1968–1977.

  • Gutterman JU. . 1994 Proc. Natl. Acad. Sci. USA 91: 1198–1205.

  • Hu P, Margolis B and Schlessinger J. . 1993 Bioessays 15: 179–183.

  • Katzav S, Martin-Zanca D and Barbacid M. . 1989 EMBO J. 8: 2283–2290.

  • Katzav S. . 1995 Crit. Rev. Oncog. 6: 82–97.

  • Komatsu N, Nakauchi H, Miwa A, Ishihara T, Egushi M, Moroi M, Okada Sato Y, Wada H, Yawata Y, Suda T and Miura Y. . 1991 Cancer Res. 51: 341–348.

  • Lewerenz M, Mogensen KE and Uzé G. . 1998 J. Mol. Biol. 282: 585–599.

  • Lutfalla G, Holland SJ, Cinato E, Monneron D, Reboul J, Rogers NC, Smith JM, Stark GR, Gardiner K, Mogensen KE, Kerr IM and Uzé G. . 1995 EMBO J. 14: 5100–5108.

  • Luger SM, Ratajczak J, Ratajczak MZ, Kuczynski WI, Di Paola RS, Ngo W, Clevenger CV and Gewirtz AM. . 1996 Blood 87: 1326–1334.

  • Martyré M-C and Wietzerbin J. . 1994 Br. J. Haematol. 86: 244–252.

  • Matsuguchi T, Inhorn RC, Carlesso N, Xu G, Druker B and Griffin JD. . 1995 EMBO J. 14: 257–265.

  • Miura O, Miura Y, Nakamura N, Quelle FW, Witthuhn BA, Ihle JN and Aoki N. . 1994 Blood 84: 4135–4141.

  • Miyakawa Y, Oda A, Druker BJ, Ozaki K, Handa M, Ohashi H and Ikeda Y. . 1997 Blood 89: 2789–2798.

  • Novick D, Cohen B and Rubinstein M. . 1994 Cell 77: 391–400.

  • Platanias LC and Sweet ME. . 1994 J. Biol. Chem. 269: 3143–3146.

  • Reeves WH, Satoh M, Wang J and Ajmani AK. . 1994 Manual of Biological Markers of Disease. 1-22 van Venrooij WJ and Maini RN (eds).. Kluwer Academic Publishers: Dordrecht, The Netherlands.

    Google Scholar 

  • Romero F, Dargemont C, Pozo F, Reeves WH, Camonis J, Gisselbrecht S and Fisher S. . 1996 Mol. Cell. Biol. 16: 37–44.

  • Romero F and Fischer S. . 1996 Cell. Signal. 8: 545–553.

  • Romero F, Germani A, Puvion E, Camonis J, Varin-Blank N, Gisselbrecht S and Fischer S. . 1998 J. Biol. Chem. 273: 5923–5931.

  • Sacchi S. . 1995 Leukemia Lymphoma 19: 13–20.

  • Sanceau J, Kaisho T, Hirano T and Wietzerbin J. . 1995 J. Biol. Chem. 270: 27920–27931.

  • Talpaz M, Kantarjian HM, McCredie K, Trujillo JM, Keating MJ and Gutterman JU. . 1986 New Engl. J. Med. 314: 1065–1069.

  • Tarakhovsky A, Turner M, Schaal S, Mee PJ, Duddy LP, Rajewsky K and Tybulewicz VL. . 1995 Nature 374: 467–470.

  • Uddin S, Sweet M, Colamonci OR, Krolewski JJ and Platanias LC. . 1997 FEBS Letters 403: 31–34.

  • Uzé G, Lutfalla G and Gresser I. . 1990 Cell 60: 225–234.

  • Velazquez L, Mogensen KE, Barbieri G, Fellous M, Uzé G and Pellegrini S. . 1995 J. Biol. Chem. 270: 3327–3334.

  • Williams BRG and Haque SJ. . 1997 Semin. Oncol. 24: S9-70–S9-77.

  • Wu J, Katzav S and Weiss A. . 1995 Mol. Cell. Biol. 15: 4337–4346.

  • Zhang R, Alt FW, Davidson L, Orkin SH and Swatt W. . 1995 Nature 374: 470–473.

Download references

Acknowledgements

This work was supported by the Reseau de Recherche Clinique INSERM no 4R006C and a grant from ARC no 9806.

Author information

Authors and Affiliations

  1. Unité 365 INSERM, Institut Curie, Section Recherche, 26 rue d'Ulm, Paris, 75231, France

    Anne Micouin, Juana Wietzerbin, Virginie Steunou & Marie-Claire Martyré

Authors
  1. Anne Micouin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juana Wietzerbin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Virginie Steunou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marie-Claire Martyré
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Micouin, A., Wietzerbin, J., Steunou, V. et al. p95vav associates with the type I interferon (IFN) receptor and contributes to the antiproliferative effect of IFN-α in megakaryocytic cell lines. Oncogene 19, 387–394 (2000). https://doi.org/10.1038/sj.onc.1203314

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203314

Keywords

This article is cited by

Search

Advanced search

Quick links