Current Biology
Volume 9, Issue 4, 25 February 1999, Pages 215-218
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Brief Communications
Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR

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Abstract

The tumor necrosis factor (TNF) and TNF receptor (TNFR) gene superfamilies regulate diverse biological functions, including cell proliferation, differentiation, and survival [1][2][3]. We have identified a new TNF-related ligand, designated human GITR ligand (hGITRL), and its human receptor (hGITR), an ortholog of the recently discovered murine glucocorticoid-induced TNFR-related (mGITR) protein [4]. The hGITRL gene mapped to chromosome 1q23, near the gene for the TNF homolog Fas/CD95 ligand [5]. The hGITR gene mapped to chromosome 1p36, near a cluster of five genes encoding TNFR homologs [1], [6]. We found hGITRL mRNA in several peripheral tissues, and detected hGITRL protein on cultured vascular endothelial cells. The levels of hGITR mRNA in tissues were generally low; in peripheral blood T cells, however, antigen-receptor stimulation led to a substantial induction of hGITR transcripts. Cotransfection of hGITRL and hGITR in embryonic kidney 293 cells activated the anti-apoptotic transcription factor NF-κB, via a pathway that appeared to involve TNFR-associated factor 2 (TRAF2) [7] and NF-κB-inducing kinase (NIK) [8]. Cotransfection of hGITRL and hGITR in Jurkat T leukemia cells inhibited antigen-receptor-induced cell death. Thus, hGITRL and hGITR may modulate T lymphocyte survival in peripheral tissues.

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AL Gurney, A Huang, RM Pitti, M Mark, DT Baldwin, AM Gray, P Dowd, J Brush, S Heldens, AD Goddard, WI Wood, KP Baker and PJ Godowski, Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.

SA Marsters, P Schow and A Ashkenazi, Department of Molecular Oncology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.

E-mail address for A Ashkenazi (corresponding author): [email protected].

A.L.G. and S.A.M. contributed equally to this work.