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

Autor: A. Gurney, R.M. Pitti, Melanie R. Mark, Arthur J Huang, Alane M. Gray, Patrick Dowd, Paulj. Godowski, S. Marsters, K.P. Baker, Daryl T. Baldwin, A.D. Goddard, Jennifer Brush, Peter Schow, Sherry Heldens, Avi Ashkenazi, William I. Wood
Rok vydání: 1999
Předmět:
TRAF2
Transcription
Genetic
Molecular Sequence Data
Receptors
Nerve Growth Factor
Biology
Vascular endothelial growth inhibitor
Transfection
Jurkat cells
General Biochemistry
Genetics and Molecular Biology
Receptors
Tumor Necrosis Factor
Cell Line
Glucocorticoid-Induced TNFR-Related Protein
Mice
Animals
Humans
Amino Acid Sequence
RNA
Messenger
Transcription factor
Cells
Cultured
Regulation of gene expression
Sequence Homology
Amino Acid
Agricultural and Biological Sciences(all)
Tumor Necrosis Factor-alpha
Biochemistry
Genetics and Molecular Biology(all)
HEK 293 cells
Chromosome Mapping
Proteins
TNF Receptor-Associated Factor 2
Molecular biology
Recombinant Proteins
Gene Expression Regulation
Chromosomes
Human
Pair 1
Multigene Family
Tumor necrosis factor alpha
Endothelium
Vascular
General Agricultural and Biological Sciences
Sequence Alignment
Signal Transduction
Zdroj: Current Biology. 9(4):215-218
ISSN: 0960-9822
DOI: 10.1016/s0960-9822(99)80093-1
Popis: 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-kappaB, via a pathway that appeared to involve TNFR-associated factor 2 (TRAF2) [7] and NF-kappaB-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.
Databáze: OpenAIRE
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