Lymphotoxin beta receptor explained

Lymphotoxin beta receptor (LTBR), also known as tumor necrosis factor receptor superfamily member 3 (TNFRSF3), is a cell surface receptor for lymphotoxin involved in apoptosis and cytokine release.^{[1] [2] [3]} It is a member of the tumor necrosis factor receptor superfamily.

Function

The protein encoded by this gene is a member of the tumor necrosis factor (TNF) family of receptors. It is expressed on the surface of most cell types, including cells of epithelial and myeloid lineages, but not on T and B lymphocytes. The protein specifically binds the lymphotoxin membrane form (a complex of lymphotoxin-alpha and lymphotoxin-beta). The encoded protein and its ligand play a role in the development and organization of lymphoid tissue and transformed cells. Activation of the encoded protein can trigger apoptosis.^[1]

Not only does the LTBR help trigger apoptosis, it can lead to the release of the cytokine interleukin 8. Overexpression of LTBR in HEK293 cells increases IL-8 promoter activity and leads to IL-8 release. LTBR is also essential for development and organization of the secondary lymphoid organs and chemokine release.^[4]

Structure

The Ramachandran plots show that 64.6% of all residues were in a favored region.This structure was found using X-ray diffraction. The resolution is 3.50 angstroms.The alpha and beta angles are 90 degrees while the gamma angle is 120 degrees.^[5]

Interactions

Lymphotoxin beta receptor has been shown to interact with Diablo homolog^[6] and TRAF3.^{[7] [8] [9]}

Further reading

• Elewaut D, Ware CF . The unconventional role of LT alpha beta in T cell differentiation. . Trends Immunol. . 28 . 4 . 169–75 . 2007 . 17336158 . 10.1016/j.it.2007.02.005 .
• Browning JL, Ngam-ek A, Lawton P, etal . Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface. . Cell . 72 . 6 . 847–56 . 1993 . 7916655 . 10.1016/0092-8674(93)90574-A . 28961163 .
• Crowe PD, VanArsdale TL, Walter BN, etal . A lymphotoxin-beta-specific receptor. . Science . 264 . 5159 . 707–10 . 1994 . 8171323 . 10.1126/science.8171323 . 1994Sci...264..707C .
• Baens M, Chaffanet M, Cassiman JJ, etal . Construction and evaluation of a hncDNA library of human 12p transcribed sequences derived from a somatic cell hybrid. . Genomics . 16 . 1 . 214–8 . 1993 . 8486360 . 10.1006/geno.1993.1161 .
• Baens M, Aerssens J, van Zand K, etal . Isolation and regional assignment of human chromosome 12p cDNAs. . Genomics . 29 . 1 . 44–52 . 1996 . 8530100 . 10.1006/geno.1995.1213 .
• Wang X, Bornslaeger EA, Haub O, etal . A candidate gene for the amnionless gastrulation stage mouse mutation encodes a TRAF-related protein. . Dev. Biol. . 177 . 1 . 274–90 . 1996 . 8660894 . 10.1006/dbio.1996.0162 . free .
• Nakano H, Oshima H, Chung W, etal . TRAF5, an activator of NF-kappaB and putative signal transducer for the lymphotoxin-beta receptor. . J. Biol. Chem. . 271 . 25 . 14661–4 . 1996 . 8663299 . 10.1074/jbc.271.25.14661 . free .
• Matsumoto M, Hsieh TY, Zhu N, etal . Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin-beta receptor. . J. Virol. . 71 . 2 . 1301–9 . 1997 . 8995654 . 10.1128/JVI.71.2.1301-1309.1997. 191185 .
• VanArsdale TL, VanArsdale SL, Force WR, etal . Lymphotoxin-beta receptor signaling complex: role of tumor necrosis factor receptor-associated factor 3 recruitment in cell death and activation of nuclear factor kappaB. . Proc. Natl. Acad. Sci. U.S.A. . 94 . 6 . 2460–5 . 1997 . 9122217 . 10.1073/pnas.94.6.2460 . 20110 . 1997PNAS...94.2460V . free .
• Wu MY, Hsu TL, Lin WW, etal . Serine/threonine kinase activity associated with the cytoplasmic domain of the lymphotoxin-beta receptor in HepG2 cells. . J. Biol. Chem. . 272 . 27 . 17154–9 . 1997 . 9202035 . 10.1074/jbc.272.27.17154 . free .
• Chen CM, You LR, Hwang LH, Lee YH . Direct interaction of hepatitis C virus core protein with the cellular lymphotoxin-beta receptor modulates the signal pathway of the lymphotoxin-beta receptor. . J. Virol. . 71 . 12 . 9417–26 . 1997 . 9371602 . 10.1128/JVI.71.12.9417-9426.1997. 230246 .
• Mizushima S, Fujita M, Ishida T, etal . Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5). . Gene . 207 . 2 . 135–40 . 1998 . 9511754 . 10.1016/S0378-1119(97)00616-1 .
• Krajewska M, Krajewski S, Zapata JM, etal . TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues. . Am. J. Pathol. . 152 . 6 . 1549–61 . 1998 . 9626059 . 1858434 .
• Boussaud V, Soler P, Moreau J, etal . Expression of three members of the TNF-R family of receptors (4-1BB, lymphotoxin-beta receptor, and Fas) in human lung. . Eur. Respir. J. . 12 . 4 . 926–31 . 1999 . 9817170 . 10.1183/09031936.98.12040926 . free .
• Murphy M, Walter BN, Pike-Nobile L, etal . Expression of the lymphotoxin beta receptor on follicular stromal cells in human lymphoid tissues. . Cell Death Differ. . 5 . 6 . 497–505 . 1999 . 10200501 . 10.1038/sj.cdd.4400374 . free .
• Wu MY, Wang PY, Han SH, Hsieh SL . The cytoplasmic domain of the lymphotoxin-beta receptor mediates cell death in HeLa cells. . J. Biol. Chem. . 274 . 17 . 11868–73 . 1999 . 10207006 . 10.1074/jbc.274.17.11868 . free .
• Yu KY, Kwon B, Ni J, etal . A newly identified member of tumor necrosis factor receptor superfamily (TR6) suppresses LIGHT-mediated apoptosis. . J. Biol. Chem. . 274 . 20 . 13733–6 . 1999 . 10318773 . 10.1074/jbc.274.20.13733 . free .
• Rooney IA, Butrovich KD, Glass AA, etal . The lymphotoxin-beta receptor is necessary and sufficient for LIGHT-mediated apoptosis of tumor cells. . J. Biol. Chem. . 275 . 19 . 14307–15 . 2000 . 10799510 . 10.1074/jbc.275.19.14307 . free .
• Langeggen H, Berge KE, Johnson E, Hetland G . Human umbilical vein endothelial cells express complement receptor 1 (CD35) and complement receptor 4 (CD11c/CD18) in vitro. . Inflammation . 26 . 3 . 103–10 . 2003 . 12083416 . 10.1023/A:1015585530204 . 54700 .
• Chang YH, Hsieh SL, Chen MC, Lin WW . Lymphotoxin beta receptor induces interleukin 8 gene expression via NF-kappaB and AP-1 activation. . Exp. Cell Res. . 278 . 2 . 166–74 . 2002 . 12169272 . 10.1006/excr.2002.5573 .

Notes and References

1. Web site: Entrez Gene: LTBR lymphotoxin beta receptor (TNFR superfamily, member 3).
2. Baens M, Chaffanet M, Cassiman JJ, van den Berghe H, Marynen P . Construction and evaluation of a hncDNA library of human 12p transcribed sequences derived from a somatic cell hybrid . Genomics . 16 . 1 . 214–8 . April 1993 . 8486360 . 10.1006/geno.1993.1161 .
3. Crowe PD, VanArsdale TL, Walter BN, Ware CF, Hession C, Ehrenfels B, Browning JL, Din WS, Goodwin RG, Smith CA . A lymphotoxin-beta-specific receptor . Science . 264 . 5159 . 707–10 . April 1994 . 8171323 . 10.1126/science.8171323 . 1994Sci...264..707C .
4. Chang YH, Hsieh SL, Chen MC, Lin WW . Lymphotoxin beta receptor induces interleukin 8 gene expression via NF-kappaB and AP-1 activation . Exp. Cell Res. . 278 . 2 . 166–74 . August 2002 . 12169272 . 10.1006/excr.2002.5573 .
5. Web site: MolProbity Ramachandran analysis . https://web.archive.org/web/20121012104917/http://www.rcsb.org/pdb/images/1RF3_ram_m_500.pdf . 2012-10-12 . dead .
6. Kuai . Jun . Nickbarg Elliott . Wooters Joe . Qiu Yongchang . Wang Jack . Lin Lih-Ling . Apr 2003 . Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis . J. Biol. Chem. . 278 . 16 . 14363–9 . United States. 0021-9258. 12571250 . 10.1074/jbc.M208672200 . free .
7. 10.1073/pnas.94.6.2460 . VanArsdale . T L . VanArsdale S L . Force W R . Walter B N . Mosialos G . Kieff E . Reed J C . Ware C F . Elliott D. Kieff. Mar 1997 . Lymphotoxin-beta receptor signaling complex: role of tumor necrosis factor receptor-associated factor 3 recruitment in cell death and activation of nuclear factor kappaB . . 94 . 6 . 2460–5 . UNITED STATES. 0027-8424. 9122217 . 1997PNAS...94.2460V . 20110 . free .
8. 10.1074/jbc.274.17.11868 . Wu . M Y . Wang P Y . Han S H . Hsieh S L . Apr 1999 . The cytoplasmic domain of the lymphotoxin-beta receptor mediates cell death in HeLa cells . J. Biol. Chem. . 274 . 17 . 11868–73 . UNITED STATES. 0021-9258. 10207006 . free .
9. 10.1074/jbc.272.22.14029 . Marsters . S A . Ayres T M . Skubatch M . Gray C L . Rothe M . Ashkenazi A . May 1997 . Herpesvirus entry mediator, a member of the tumor necrosis factor receptor (TNFR) family, interacts with members of the TNFR-associated factor family and activates the transcription factors NF-kappaB and AP-1 . J. Biol. Chem. . 272 . 22 . 14029–32 . UNITED STATES. 0021-9258. 9162022 . free .