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Journal of Virology, February 2005, p. 2325-2334, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2325-2334.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Disruption of the Shc/Grb2 Complex during Abelson Virus Transformation Affects Proliferation, but Not Apoptosis

Linda B. Baughn1,2 and Naomi Rosenberg1,2,3*

Immunology Graduate Program,1 Departments of Pathology,2 Molecular Biology and Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts3

Received 23 July 2004/ Accepted 29 September 2004

The v-Abl protein tyrosine kinase encoded by Abelson murine leukemia virus (Ab-MLV) induces pre-B-cell transformation. Signals emanating from the SH2 domain of the protein are required for transformation, and several proteins bind this region of v-Abl. One such protein is the adaptor molecule Shc, a protein that complexes with Grb2/Sos and facilitates Ras activation, an event associated with Ab-MLV transformation. To test the role this interaction plays in growth and survival of infected pre-B cells, dominant-negative (DN) Shc proteins were coexpressed with v-Abl and transformation was examined. Expression of DN Shc reduced Ab-MLV pre-B-cell transformation and decreased the ability of v-Abl to stimulate Ras activation and Erk phosphorylation in a Raf-dependent but Rac-independent fashion. Further analysis revealed that Shc is required for v-Abl-mediated Raf tyrosine 340 and 341 phosphorylation, an event associated with Erk phosphorylation. In contrast to effects on proliferation, survival of the cells and activation of Akt were not affected by expression of DN Shc. Together, these data reveal that v-Abl-Shc interactions are a critical part of the growth stimulatory signals delivered during transformation but that they do not affect antiapoptotic pathways. Furthermore, these data highlight a novel role for Shc in signaling from v-Abl to Raf.

* Corresponding author. Mailing address: Jaharis 808, Tufts Medical School, 150 Harrison Ave., Boston, MA 02111. Phone: (617) 636-2143. Fax: (617) 636-0337. E-mail: naomi.rosenberg{at}tufts.edu.

Journal of Virology, February 2005, p. 2325-2334, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2325-2334.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zimmerman, R. S., Rosenberg, N. (2008). Changes in p19Arf Localization Accompany Apoptotic Crisis during Pre-B-Cell Transformation by Abelson Murine Leukemia Virus. J. Virol. 82: 8383-8391 [Abstract] [Full Text]  
  • Radhakrishnan, Y., Maile, L. A., Ling, Y., Graves, L. M., Clemmons, D. R. (2008). Insulin-like Growth Factor-I Stimulates Shc-dependent Phosphatidylinositol 3-Kinase Activation via Grb2-associated p85 in Vascular Smooth Muscle Cells. J. Biol. Chem. 283: 16320-16331 [Abstract] [Full Text]  
  • Yi, C.-r., Rosenberg, N. (2008). Mutations Affecting the MA Portion of the v-Abl Protein Reveal a Conserved Role of Gag in Abelson Murine Leukemia Virus (MLV) and Moloney MLV. J. Virol. 82: 5307-5315 [Abstract] [Full Text]  
  • Yi, C.-R., Rosenberg, N. (2007). Gag Influences Transformation by Abelson Murine Leukemia Virus and Suppresses Nuclear Localization of the v-Abl Protein. J. Virol. 81: 9461-9468 [Abstract] [Full Text]  


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