title: Characterization of human homologue of 4-1BB and its ligand.
abstract: The human homologue of 4-1BB (H4-1BB) cDNA was isolated from PMA plus ionomycin-treated human peripheral T-cell cDNA libraries. The amino acid sequence deduced from the nucleotide sequence showed that the protein is composed of 255 amino acids with 2 potential N-linked glycosylation sites. The molecular weight of its protein backbone is calculated to be 27 kDa. The H4-1BB contains features such as signal sequence and transmembrane domain, indicating that it is a receptor protein. This protein showed 60% identity of amino acid sequence to mouse 4-1BB. In the cytoplasmic domain there are 5 regions of amino acid sequences conserved from mouse to human, indicating that these residues might be important in the 4-1BB function. H4-1BB mRNA was detected in unstimulated peripheral blood T cells and was inducible in T-cell lines such as Jurkat and CEM. H4-1BB-AP, a fusion protein between the H4-1BB extracellular domain and alkaline phosphatase, was used to identify the ligand for the H4-1BB. Although the H4-1BB ligand was detected in both T and B cells of human peripheral blood, the ligand was preferentially expressed in primary B cells and B-cell lines. Daudi, a B-cell lymphoma, was one of the B-cell lines that carried a higher number of ligands. Scatchard analysis showed that the Kd = 1.4 x 10(9) M and the number of ligands in Daudi cell was 4.2 x 10(3).
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 56202-5120, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Hurtado
authors.forename: Z H
authors.initials: ZH
authors.lastname: Lee
authors.forename: K K
authors.initials: KK
authors.lastname: Kim
authors.forename: K E
authors.initials: KE
authors.lastname: Pollok
authors.forename: B S
authors.initials: BS
authors.lastname: Kwon
mesh_terms: D016475:3T3 Cells; D053330:4-1BB Ligand; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry*
chemical_list: D053330:4-1BB Ligand; D015703:Antigens, CD; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C505714:TNFRSF9 protein, human; C505974:TNFSF9 protein, human; C505715:Tnfrsf9 protein, mouse; C505975:Tnfsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha