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p66SHC promotes apoptosis and antagonizes mitogenic signaling in T cells.

Authors :
Pacini S
Pellegrini M
Migliaccio E
Patrussi L
Ulivieri C
Ventura A
Carraro F
Naldini A
Lanfrancone L
Pelicci P
Baldari CT
Source :
Molecular and cellular biology [Mol Cell Biol] 2004 Feb; Vol. 24 (4), pp. 1747-57.
Publication Year :
2004

Abstract

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.

Details

Language :
English
ISSN :
0270-7306
Volume :
24
Issue :
4
Database :
MEDLINE
Journal :
Molecular and cellular biology
Publication Type :
Academic Journal
Accession number :
14749389
Full Text :
https://doi.org/10.1128/MCB.24.4.1747-1757.2004