TI  - Identification of a new member of the tumor necrosis factor family and its
      receptor, a human ortholog of mouse GITR.
PG  - 215-8
AB  - 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 <prot>GITR ligand</prot> (<prot>hGITRL</prot> ), and its human
      receptor (<prot>hGITR</prot>) , an ortholog of the recently discovered murine <prot>glucocorticoid-induced TNFR-related (<prot>mGITR</prot>) protein</prot> [4]. The <prot>hGITRL</prot> gene
      mapped to chromosome 1q23, near the gene for the TNF homolog <prot>Fas</prot>/<prot>CD95
      ligand</prot> [5]. The <prot>hGITR</prot> gene mapped to chromosome 1p36, near a cluster of
      five genes encoding TNFR homologs [1] [6]. We found <prot>hGITRL</prot> mRNA in several
      peripheral tissues, and detected <prot>hGITRL</prot> protein on cultured vascular
      endothelial cells. The levels of <prot>hGITR</prot> mRNA in tissues were generally low;
      in peripheral blood T cells, however, antigen-receptor stimulation led to
      a substantial induction of <prot>hGITR</prot> transcripts. Cotransfection of <prot>hGITRL</prot> and
      <prot>hGITR</prot> in embryonic kidney 293 cells activated the anti-apoptotic
      transcription factor <prot>NF-kappaB</prot>, via a pathway that appeared to involve
      <prot>TNFR-associated factor 2</prot> (<prot>TRAF2</prot>) [7] and <prot><prot>NF-kappaB</prot>-inducing kinase</prot> (<prot>NIK</prot>)
      [8]. Cotransfection of <prot>hGITRL</prot> and <prot>hGITR</prot> in Jurkat T leukemia cells
      inhibited antigen-receptor-induced cell death. Thus, <prot>hGITRL</prot> and <prot>hGITR</prot> may
      modulate T lymphocyte survival in peripheral tissues.
AD  - Department of Molecular Biology Genentech Inc. 1 DNA Way South San
