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Brief Definitive Report

Francesc Marti^a, Nicholas H. Post^a, Elena Chan^a, and Philip D. King^a

^a T Cell Signaling Laboratory, Hospital for Special Surgery, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, New York 10021
T Cell Signaling Laboratory, Hospital for Special Surgery, 535 East 70th St., New York, NY 10021.212-717-1192212-774-2395

kingp{at}hss.edu

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 fraction 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 TSAd can act as a potent transcriptional activator in T cells. Furthermore, the TSAd 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 B (NF-B), 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.

Key Words: transcription • T lymphocyte • interleukin 2 • signal transduction • SH2 domain

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