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Titolo:
A transcription function for the T cell-specific adapter (TSAd) protein inT cells: Critical role of the TSAd Src homology 2 domain
Autore:
Marti, F; Post, NH; Chan, E; King, PD;
Indirizzi:
Cornell Univ, Hosp Special Surg, Weill Med Coll, T Cell Signaling Lab, NewYork, NY 10021 USA Cornell Univ New York NY USA 10021 l Signaling Lab, NewYork, NY 10021 USA Cornell Univ, Grad Sch Med Sci, New York, NY 10021 USA Cornell Univ New York NY USA 10021 ad Sch Med Sci, New York, NY 10021 USA
Titolo Testata:
JOURNAL OF EXPERIMENTAL MEDICINE
fascicolo: 12, volume: 193, anno: 2001,
pagine: 1425 - 1430
SICI:
0022-1007(20010618)193:12<1425:ATFFTT>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAMMALIAN-CELLS; GENE; NUCLEAR; CD28;
Keywords:
transcription; T lymphocyte; interleukin 2; signal transduction; SH2 domain;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
17
Recensione:
Indirizzi per estratti:
Indirizzo: King, PD Cornell Univ, Hosp Special Surg, Weill Med Coll, T Cell SignalingLab, 535E 70th St, New York, NY 10021 USA Cornell Univ 535 E 70th St New York NY USA 10021 rk, NY 10021 USA
Citazione:
F. Marti et al., "A transcription function for the T cell-specific adapter (TSAd) protein inT cells: Critical role of the TSAd Src homology 2 domain", J EXP MED, 193(12), 2001, pp. 1425-1430

Abstract

T cell-specific adapter (TSAd) protein is an Src homology 2 (SH2) domain-containing adapter molecule implicated in T cell receptor for antigen (TCR)-mediated interleukin 2 (IL-2) secretion in T cells. Here, we demonstrate that a substantial fi-action of TSAd is found in the T cell nucleus. Nuclear import of TSAd is an active process that depends on TSAd SH2 domain recognition of a phosphotyrosine-containing ligand. Importantly, we show that TSAdcan act as a potent transcriptional activator in T cells. Furthermore, theTSAd SH2 domain appears to be essential for this transcription-activating function independent of its role in nuclear import. Biochemical analyses suggest that a single TSAd SH2 domain ligand of 95-100 kD may be involved in these processes. Consistent with a role as a transcription activator, cotransfection of TSAd with an IL-2 promoter-reporter gene construct results in a considerable upregulation of IL-2 promoter activity. Further, we show that this augmentation requires a functional TSAd SH2 domain. However, TSAd does not appear to modulate the activity of-the major recognized IL-2 gene transcription factors, nuclear factor kappaB (NF-kappaB), nuclear factor of activated T cells (NFAT), or activator protein 1 (AP-1). These findings point to the function of TSAd as a novel transcription-regulatory protein in T cells and illustrate the importance of the TSAd SH2 domain in this role.

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Documento generato il 31/03/20 alle ore 04:16:27