p66SHC Promotes Apoptosis and Antagonizes Mitogenic Signaling in T Cells?

Sonia Pacini, Michela Pellegrini, Enrica Migliaccio, Laura Patrussi, Cristina Ulivieri, Andrea Ventura, Fabio Carraro, Antonella Naldini, Luisa Lanfrancone, Piergiuseppe Pelicci, Cosima T. Baldari

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1747-1757
Number of pages11
JournalMolecular and Cellular Biology
Issue number4
Publication statusPublished - Feb 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology


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