Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand.
Among members of the tumor necrosis factor receptor (TNFR) superfamily, 4-1BB, CD27, and glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) share a striking homology in the cytoplasmic domain. Here we report the identification of a new member, activation-inducible TNFR family member (AITR), which belongs to this subfamily, and its ligand. The receptor is expressed in lymph node and peripheral blood leukocytes, and its expression is up-regulated in human peripheral mononuclear cells mainly after stimulation with anti-CD3/CD28 monoclonal antibodies or phorbol 12-myristate 13-acetate/ionomycin. AITR associates with TRAF1 (TNF receptor-associated factor 1), TRAF2, and TRAF3, and induces nuclear factor (NF)-kappaB activation via TRAF2. The ligand for AITR (AITRL) was found to be an undescribed member of the TNF family, which is expressed in endothelial cells. Thus, AITR and AITRL seem to be important for interactions between activated T lymphocytes and endothelial cells.
Kwon
B
B
Department of Microbiology and Immunology and the Walther Oncology Center, Indiana University School of Medicine and the Walther Cancer Institute, Indianapolis, Indiana 46202, USA.
Yu
K Y
KY
Ni
J
J
Yu
G L
GL
Jang
I K
IK
Kim
Y J
YJ
Xing
L
L
Liu
D
D
Wang
S X
SX
Kwon
B S
BS
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D008198:Lymph Nodes / Q000378:metabolism; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics*; D016415:Sequence Alignment
D018076:DNA, Complementary; D008024:Ligands; D018124:Receptors, Tumor Necrosis Factor