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 Article
  • Published:

GRB2-mediated recruitment of GAB2, but not GAB1, to SF-STK supports the expansion of Friend virus-infected erythroid progenitor cells

Oncogene volume 25, pages 2433–2443 (2006)Cite this article

Abstract

Friend virus induces the development of erythroleukemia in mice through the interaction of a viral glycoprotein, gp55, with a truncated form of the Stk receptor tyrosine kinase, short form-Stk (Sf-Stk), and the EpoR. We have shown previously that the ability of Sf-Stk to participate in the transformation of Friend virus-infected cells requires the kinase activity and Grb2-binding site of Sf-Stk. Here we show that Grb2 heterozygous mice exhibit decreased susceptibility to Friend erythroleukemia and that expansion of erythroid progenitors in response to infection requires the C-terminal SH3 domain of Grb2. A fusion protein in which the Grb2-binding site in Sf-Stk is replaced by Gab2, supports the growth of progenitors from mice lacking Sf-Stk, whereas a Sf-Stk/Gab1 fusion protein does not. Gab2 is expressed in spleens from Friend virus-infected mice, co-immunoprecipitates with Sf-Stk and is tyrosine phosphorylated in the presence of Sf-Stk. Mice with a targeted deletion in Gab2 are less susceptible to Friend erythroleukemia and the expansion of erythroid progenitor cells in response to infection can be rescued by expression of Gab2, but not Gab1. Taken together, these data indicate that a Sf-Stk/Grb2/Gab2 complex mediates the growth of primary erythroid progenitor cells in response to Friend virus.

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
Figure 6
Figure 7

Similar content being viewed by others

References

  • Axelrad A . (1969). Proc Can Cancer Conf 8: 313–343.

  • Bausenwein BS, Schmidt M, Mielke B, Raabe T . (2000). Mech Dev 90: 205–215.

  • Behringer RR, Dewey MJ . (1985). Cell 40: 441–447.

  • Ben-David Y, Bernstein A . (1991). Cell 66: 831–834.

  • Bladt F, Riethmacher D, Isenmann S, Aguzzi A, Birchmeier C . (1995). Nature 376: 768–771.

  • Cheng AM, Saxton TM, Sakai R, Kulkarni S, Mbamalu G, Vogel W et al. (1998). Cell 95: 793–803.

  • Cunnick JM, Mei L, Doupnik CA, Wu J . (2001). J Biol Chem 276: 24380–24387, Epub 2001 Apr 25.

  • D'Andrea AD . (1992). Cancer Surv 15: 19–36.

  • Dickson B, Sprenger F, Morrison D, Hafen E . (1992). Nature 360: 600–603.

  • Feng GS . (1999). Exp Cell Res 253: 47–54.

  • Finkelstein LD, Ney PA, Liu QP, Paulson RF, Correll PH . (2002). Oncogene 21: 3562–3570.

  • Fournier T, Kamikura D, Teng K, Park M . (1996). J Biol Chem 271: 22211–22217.

  • Gong Q, Cheng AM, Akk AM, Alberola-Ila J, Gong G, Pawson T et al. (2001). Nat Immunol 2: 29–36.

  • Gu H, Maeda H, Moon JJ, Lord JD, Yoakim M, Nelson BH et al. (2000). Mol Cell Biol 20: 7109–7120.

  • Gu H, Neel BG . (2003). Trends Cell Biol 13: 122–130.

  • Gu H, Saito K, Klaman LD, Shen J, Fleming T, Wang Y et al. (2001). Nature 412: 186–190.

  • Hayman MJ, Kitchener G, Vogt PK, Beug H . (1985). Proc Natl Acad Sci USA 82: 8237–8241.

  • Herbst R, Carroll PM, Allard JD, Schilling J, Raabe T, Simon MA . (1996). Cell 85: 899–909.

  • Herbst R, Zhang X, Qin J, Simon MA . (1999). EMBO J 18: 6950–6961.

  • Hibi M, Hirano T . (2000). Leuk Lymphoma 37: 299–307.

  • Horoszewicz JS, Leong SS, Carter WA . (1975). J Natl Cancer Inst 54: 265–267.

  • Isakoff SJ, Cardozo T, Andreev J, Li Z, Ferguson KM, Abagyan R et al. (1998). EMBO J 17: 5374–5387.

  • Ischenko I, Petrenko O, Gu H, Hayman MJ . (2003). Oncogene 22: 6311–6318.

  • Kohda D, Terasawa H, Ichikawa S, Ogura K, Hatanaka H, Mandiyan V et al. (1994). Structure 2: 1029–1040.

  • Lecoq-Lafon C, Verdier F, Fichelson S, Chretien S, Gisselbrecht S, Lacombe C et al. (1999). Blood 93: 2578–2585.

  • Lewitzky M, Kardinal C, Gehring NH, Schmidt EK, Konkol B, Eulitz M et al. (2001). Oncogene 20: 1052–1062.

  • Li JP, D'Andrea AD, Lodish HF, Baltimore D . (1990). Nature 343: 762–764.

  • Liao SK, Axelrad AA . (1975). Int J Cancer 15: 467–482.

  • Lilly F . (1970). J Natl Cancer Inst 45: 163–169.

  • Liu Y, Rohrschneider LR . (2002). FEBS Lett 515: 1–7.

  • Lock LS, Royal I, Naujokas MA, Park M . (2000). J Biol Chem 275: 31536–31545.

  • Maroun CR, Holgado-Madruga M, Royal I, Naujokas MA, Fournier TM, Wong AJ et al. (1999a). Mol Cell Biol 19: 1784–1799.

  • Maroun CR, Moscatello DK, Naujokas MA, Holgado-Madruga M, Wong AJ, Park M . (1999b). J Biol Chem 274: 31719–31726.

  • Maroun CR, Naujokas MA, Holgado-Madruga M, Wong AJ, Park M . (2000). Mol Cell Biol 20: 8513–8525.

  • Mirand EA, Steeves RA, Lange RD, Grace Jr JT . (1968). Proc Soc Exp Biol Med 128: 844–849.

  • Moreau-Gachelin F, Tavitian A, Tambourin P . (1988). Nature 331: 277–280.

  • Mowat M, Cheng A, Kimura N, Bernstein A, Benchimol S . (1985). Nature 314: 633–636.

  • Neel BG, Gu H, Pao L . (2003). Trends Biochem Sci 28: 284–293.

  • Nishigaki K, Hanson C, Ohashi T, Thompson D, Muszynski K, Ruscetti S . (2000). J Virol 74: 3037–3045.

  • Nishigaki K, Thompson D, Hanson C, Yugawa T, Ruscetti S . (2001). J Virol 75: 7893–7903.

  • Park C, Hayman M . (1999). J Biol Chem 274: 7583–7590.

  • Persons D, Paulson R, Loyd M, Herley M, Bodner S, Bernstein A et al. (1999). Nat Genet 23: 159–165.

  • Raabe T, Riesgo-Escovar J, Liu X, Bausenwein BS, Deak P, Maroy P et al. (1996). Cell 85: 911–920.

  • Rodrigues GA, Falasca M, Zhang Z, Ong SH, Schlessinger J . (2000). Mol Cell Biol 20: 1448–1459.

  • Sachs M, Brohmann H, Zechner D, Muller T, Hulsken J, Walther I et al. (2000). J Cell Biol 150: 1375–1384.

  • Sattler M, Mohi MG, Pride YB, Quinnan LR, Malouf NA, Podar K et al. (2002). Cancer Cell 1: 479–492.

  • Saxton TM, Cheng AM, Ong SH, Lu Y, Sakai R, Cross JC et al. (2001). Curr Biol 11: 662–670.

  • Schaeper U, Gehring NH, Fuchs KP, Sachs M, Kempkes B, Birchmeier W . (2000). J Cell Biol 149: 1419–1432.

  • Schutzman JL, Borland CZ, Newman JC, Robinson MK, Kokel M, Stern MJ . (2001). Mol Cell Biol 21: 8104–8116.

  • Seiffert M, Custodio JM, Wolf I, Harkey M, Liu Y, Blattman JN et al. (2003). Mol Cell Biol 23: 2415–2424.

  • Smith DR, Vogt PK, Hayman MJ . (1989). Proc Natl Acad Sci USA 86: 5291–5295.

  • Stern MJ, Marengere LE, Daly RJ, Lowenstein EJ, Kokel M, Batzer A et al. (1993). Mol Biol Cell 4: 1175–1188.

  • Tambourin P, Wendling F . (1971). Nat New Biol 234: 230–233.

  • Uehara Y, Minowa O, Mori C, Shiota K, Kuno J, Noda T et al. (1995). Nature 373: 702–705.

  • van den Akker E, van Dijk T, Parren-van Amelsvoort M, Grossman K, Schaeper U, Toney-Early K et al. (2005). Blood 103: 4457–4465.

  • Wickrema A, Uddin S, Sharma A, Chen F, Alsayed Y, Ahmad S et al. (1999). J Biol Chem 274: 24469–24474.

  • Wigler M, Pellicer A, Silverstein S, Axel R, Urlaub G, Chasin L . (1979). Proc Natl Acad Sci USA 76: 1373–1376.

  • Wolf I, Jenkins BJ, Liu Y, Seiffert M, Custodio JM, Young P et al. (2002). Mol Cell Biol 22: 231–244.

  • Zhang S, Ren J, Khan MF, Cheng AM, Abendschein D, Muslin AJ . (2003). Arterioscler Thromb Vasc Biol 23: 1788–1793, Epub 2003 Jul 3.

  • Zhao C, Yu DH, Shen R, Feng GS . (1999). J Biol Chem 274: 19649–19654.

Download references

Acknowledgements

This work was supported by Grants NIH (R01-L66471) to PHC, NIH(R01-HL66208) to GSF, LLS scholar award to PHC and ACS (PF-01-121-LIB) to LDF.

Author information

Author notes

  1. H E Teal, S Ni and P H Correll: These authors contriuted equally to this work.

Authors and Affiliations

  1. Department of Veterinary and Biomedical Science, Center for Molecular Immunology and Infectious Disease, The Pennsylvania State University, University Park, PA, USA

    H E Teal, S Ni, J Xu, R F Paulson & P H Correll

  2. NHGRI, NIH, Bethesda, MD, USA

    L D Finkelstein

  3. Washington University, St Louis, MO, USA

    A M Cheng

  4. The Burnham Institute, San Diego, CA, USA

    G-S Feng

Authors
  1. H E Teal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L D Finkelstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A M Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R F Paulson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. G-S Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P H Correll
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P H Correll.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Teal, H., Ni, S., Xu, J. et al. GRB2-mediated recruitment of GAB2, but not GAB1, to SF-STK supports the expansion of Friend virus-infected erythroid progenitor cells. Oncogene 25, 2433–2443 (2006). https://doi.org/10.1038/sj.onc.1209288

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209288

Keywords

This article is cited by

Search

Advanced search

Quick links