Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR

• Published in: Current biology Vol. 9; no. 4; pp. 215 - 218
• Main Authors: Gurney, A.L., Marsters, S.A., Huang, A., Pitti, R.M., Mark, M., Baldwin, D.T., Gray, A.M., Dowd, P., Brush, J., Heldens, S., Schow, P., Goddard, A.D., Wood, W.I., Baker, K.P., Godowski, P.J., Ashkenazi, A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 25-02-1999
• Subjects: Amino Acid Sequence; Animals; Cell Line; Cells, Cultured; Chromosome Mapping; Chromosomes, Human, Pair 1; Endothelium, Vascular - metabolism; Gene Expression Regulation; Glucocorticoid-Induced TNFR-Related Protein; Humans; Mice; Molecular Sequence Data; Multigene Family; Proteins - metabolism; Receptors, Nerve Growth Factor - chemistry; Receptors, Nerve Growth Factor - genetics; Receptors, Nerve Growth Factor - physiology; Receptors, Tumor Necrosis Factor - chemistry; Receptors, Tumor Necrosis Factor - genetics; Receptors, Tumor Necrosis Factor - physiology; Recombinant Proteins - biosynthesis; RNA, Messenger - analysis; Sequence Alignment; Sequence Homology, Amino Acid; Signal Transduction; TNF Receptor-Associated Factor 2; Transcription, Genetic; Transfection; Tumor Necrosis Factor-alpha - chemistry; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/S0960-9822(99)80093-1

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.