This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pacini, S.
Right arrow Articles by Baldari, C. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pacini, S.
Right arrow Articles by Baldari, C. T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2004, p. 1747-1757, Vol. 24, No. 4
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.4.1747-1757.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

p66SHC Promotes Apoptosis and Antagonizes Mitogenic Signaling in T Cells{dagger}

Sonia Pacini,1,{ddagger} Michela Pellegrini,1,{ddagger} Enrica Migliaccio,2 Laura Patrussi,1 Cristina Ulivieri,1 Andrea Ventura,2 Fabio Carraro,3 Antonella Naldini,3 Luisa Lanfrancone,2 Piergiuseppe Pelicci,2 and Cosima T. Baldari1*

Department of Evolutionary Biology,1 Department of General Physiology, University of Siena, 53100 Siena,3 European Institute of Oncology, 20141 Milan, Italy2

Received 1 October 2003/ Returned for modification 11 November 2003/ Accepted 19 November 2003

Of the three Shc isoforms, p66Shc is responsible for fine-tuning p52/p46Shc signaling to Ras and has been implicated in apoptotic responses to oxidative stress. Here we show that human peripheral blood lymphocytes and mouse thymocytes and splenic T cells acquire the capacity to express p66Shc in response to apoptogenic stimulation. Using a panel of T-cell transfectants and p66Shc-/- T cells, we show that p66Shc expression results in increased susceptibility to apoptogenic stimuli, which depends on Ser36 phosphorylation and correlates with an altered balance in apoptosis-regulating gene expression. Furthermore, p66Shc blunts mitogenic responses to T-cell receptor engagement, at least in part by transdominant inhibition of p52Shc signaling to Ras/mitogen-activated protein kinases, in an S36-dependent manner. The data highlight a novel interplay between p66Shc and p52Shc in the control of T-cell fate.

* Corresponding author. Mailing address: Department of Evolutionary Biology, University of Siena, Via Aldo Moro 2, 52100 Siena, Italy. Phone: 39-0577-234400. Fax: 39-0577-234476. E-mail: baldari{at}unisi.it.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org.

{ddagger} S.P. and M.P. contributed equally to this work.

Molecular and Cellular Biology, February 2004, p. 1747-1757, Vol. 24, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.4.1747-1757.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Alam, S. M., Rajendran, M., Ouyang, S., Veeramani, S., Zhang, L., Lin, M.-F. (2009). A novel role of Shc adaptor proteins in steroid hormone-regulated cancers. Endocr Relat Cancer 16: 1-16 [Abstract] [Full Text]  
  • Natalicchio, A., De Stefano, F., Perrini, S., Laviola, L., Cignarelli, A., Caccioppoli, C., Quagliara, A., Melchiorre, M., Leonardini, A., Conserva, A., Giorgino, F. (2009). Involvement of the p66Shc protein in glucose transport regulation in skeletal muscle myoblasts. Am. J. Physiol. Endocrinol. Metab. 296: E228-E237 [Abstract] [Full Text]  
  • Savino, M. T., Ortensi, B., Ferro, M., Ulivieri, C., Fanigliulo, D., Paccagnini, E., Lazzi, S., Osti, D., Pelicci, G., Baldari, C. T. (2009). Rai Acts as a Negative Regulator of Autoimmunity by Inhibiting Antigen Receptor Signaling and Lymphocyte Activation. J. Immunol. 182: 301-308 [Abstract] [Full Text]  
  • Berniakovich, I., Trinei, M., Stendardo, M., Migliaccio, E., Minucci, S., Bernardi, P., Pelicci, P. G., Giorgio, M. (2008). p66Shc-generated Oxidative Signal Promotes Fat Accumulation. J. Biol. Chem. 283: 34283-34293 [Abstract] [Full Text]  
  • Xi, G., Shen, X., Clemmons, D. R. (2008). p66shc Negatively Regulates Insulin-Like Growth Factor I Signal Transduction via Inhibition of p52shc Binding to Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate-1 Leading to Impaired Growth Factor Receptor-Bound Protein-2 Membrane Recruitment. Mol. Endocrinol. 22: 2162-2175 [Abstract] [Full Text]  
  • Chahdi, A., Sorokin, A. (2008). Endothelin-1 Couples {beta}Pix to p66Shc: Role of {beta}Pix in Cell Proliferation through FOXO3a Phosphorylation and p27kip1 Down-Regulation Independently of Akt. Mol. Biol. Cell 19: 2609-2619 [Abstract] [Full Text]  
  • Finetti, F., Pellegrini, M., Ulivieri, C., Savino, M. T., Paccagnini, E., Ginanneschi, C., Lanfrancone, L., Pelicci, P. G., Baldari, C. T. (2008). The proapoptotic and antimitogenic protein p66SHC acts as a negative regulator of lymphocyte activation and autoimmunity. Blood 111: 5017-5027 [Abstract] [Full Text]  
  • Cosentino, F., Francia, P., Camici, G. G., Pelicci, P. G., Volpe, M., Luscher, T. F. (2008). Final Common Molecular Pathways of Aging and Cardiovascular Disease: Role of the p66Shc Protein. Arterioscler. Thromb. Vasc. Bio. 28: 622-628 [Abstract] [Full Text]  
  • Zaccagnini, G., Martelli, F., Magenta, A., Cencioni, C., Fasanaro, P., Nicoletti, C., Biglioli, P., Pelicci, P. G., Capogrossi, M. C. (2007). p66ShcA and Oxidative Stress Modulate Myogenic Differentiation and Skeletal Muscle Regeneration after Hind Limb Ischemia. J. Biol. Chem. 282: 31453-31459 [Abstract] [Full Text]  
  • Obreztchikova, M., Elouardighi, H., Ho, M., Wilson, B. A., Gertsberg, Z., Steinberg, S. F. (2006). Distinct Signaling Functions for Shc Isoforms in the Heart. J. Biol. Chem. 281: 20197-20204 [Abstract] [Full Text]  
  • Rota, M., LeCapitaine, N., Hosoda, T., Boni, A., De Angelis, A., Padin-Iruegas, M. E., Esposito, G., Vitale, S., Urbanek, K., Casarsa, C., Giorgio, M., Luscher, T. F., Pelicci, P. G., Anversa, P., Leri, A., Kajstura, J. (2006). Diabetes Promotes Cardiac Stem Cell Aging and Heart Failure, Which Are Prevented by Deletion of the p66shc Gene. Circ. Res. 99: 42-52 [Abstract] [Full Text]  
  • Menini, S., Amadio, L., Oddi, G., Ricci, C., Pesce, C., Pugliese, F., Giorgio, M., Migliaccio, E., Pelicci, P., Iacobini, C., Pugliese, G. (2006). Deletion of p66Shc Longevity Gene Protects Against Experimental Diabetic Glomerulopathy by Preventing Diabetes-Induced Oxidative Stress. Diabetes 55: 1642-1650 [Abstract] [Full Text]  
  • Khanday, F. A., Yamamori, T., Mattagajasingh, I., Zhang, Z., Bugayenko, A., Naqvi, A., Santhanam, L., Nabi, N., Kasuno, K., Day, B. W., Irani, K. (2006). Rac1 Leads to Phosphorylation-dependent Increase in Stability of the p66shc Adaptor Protein: Role in Rac1-induced Oxidative Stress. Mol. Biol. Cell 17: 122-129 [Abstract] [Full Text]  
  • Naldini, A., Bernini, C., Pucci, A., Carraro, F. (2005). Thrombin-mediated IL-10 up-regulation involves protease-activated receptor (PAR)-1 expression in human mononuclear leukocytes. J. Leukoc. Biol. 78: 736-744 [Abstract] [Full Text]  
  • Hu, Y., Wang, X., Zeng, L., Cai, D.-Y., Sabapathy, K., Goff, S. P., Firpo, E. J., Li, B. (2005). ERK Phosphorylates p66shcA on Ser36 and Subsequently Regulates p27kip1 Expression via the Akt-FOXO3a Pathway: Implication of p27kip1 in Cell Response to Oxidative Stress. Mol. Biol. Cell 16: 3705-3718 [Abstract] [Full Text]  
  • Lee, M. K., Pryhuber, G. S., Schwarz, M. A., Smith, S. M., Pavlova, Z., Sunday, M. E. (2005). Developmental Regulation of p66Shc Is Altered by Bronchopulmonary Dysplasia in Baboons and Humans. Am. J. Respir. Crit. Care Med. 171: 1384-1394 [Abstract] [Full Text]  
  • Paccani, S. R., Tonello, F., Ghittoni, R., Natale, M., Muraro, L., D'Elios, M. M., Tang, W.-J., Montecucco, C., Baldari, C. T. (2005). Anthrax toxins suppress T lymphocyte activation by disrupting antigen receptor signaling. JEM 201: 325-331 [Abstract] [Full Text]  
  • Martin, F. M., Friedman, J. S. (2004). Ticking Fast or Ticking Slow, Through Shc Must You Go?. Sci Aging Knowl Environ 2004: pe32-pe32 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»