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{{protein
{{Infobox_gene}}
|Name=tumor necrosis factor receptor superfamily, member 9
'''CD137''' is a member of the tumor necrosis factor ([[Tumor necrosis factors|TNF]]) receptor family. Its alternative names are ''tumor necrosis factor receptor superfamily member 9'' (TNFRSF9), '''4-1BB''' and ''induced by lymphocyte activation'' (ILA). It is currently of interest to immunologists as a co-stimulatory [[immune checkpoint]] molecule.
|caption=
|image=
|width=
|HGNCid=11924
|Symbol=TNFRSF9
|AltSymbols=ILA, CD137
|EntrezGene=3604
|OMIM=602250
|RefSeq=NM_001561
|UniProt=Q07011
|PDB=
|ECnumber=
|Chromosome=1
|Arm=p
|Band=36
|LocusSupplementaryData=
}}
{{SI}}
{{CMG}}


==Overview==
==Expression==
'''CD137''' is a member of the tumor necrosis factor ([[TNF]]) receptor family. Its alternative names are ''4-1BB'' and ''induced by lymphocyte activation'' (ILA).


== Expression ==
CD137 can be expressed by activated [[T cells]], but to a larger extent on [[CD8]] than on [[CD4]] [[T cells]]. In addition, CD137 expression is found on [[dendritic cells]], B cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of [[inflammation]].


CD137 can be expressed by activated [[T cells]], but to a larger extent on [[CD8]] than on [[CD4]] [[T cells]]. In addition, CD137 expression is found on [[dendritic cells]], follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of [[inflammation]].
==Specific effects on cells==


== Specific effects on cells ==
The best characterized activity of CD137 is its costimulatory activity for activated T cells. Crosslinking of CD137 enhances T cell proliferation, IL-2 secretion, survival and cytolytic activity. Further, it can enhance immune activity to eliminate tumors in mice.


The best characterized activity of CD137 is its costimulatory activity for activated T cells. Crosslinking of CD137 enhances T cell proliferatuon, IL-2 secretion survival and cytolytic activity. Further, it can enhance immune activity to eliminate tumors in mice.
== Interactions ==


==Related chapters==
CD137 has been shown to [[Protein-protein interaction|interact]] with [[TRAF2]].<ref name=pmid9464265>{{cite journal | vauthors = Jang IK, Lee ZH, Kim YJ, Kim SH, Kwon BS | title = Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B | journal = Biochem. Biophys. Res. Commun. | volume = 242 | issue = 3 | pages = 613–20 | date = Jan 1998 | pmid = 9464265 | doi = 10.1006/bbrc.1997.8016 }}</ref><ref name=pmid9418902>{{cite journal | vauthors = Arch RH, Thompson CB | title = 4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB | journal = Mol. Cell. Biol. | volume = 18 | issue = 1 | pages = 558–65 | date = Jan 1998 | pmid = 9418902 | pmc = 121523 }}</ref>
 
==As a drug target==
===Utomilumab===
[[Utomilumab]] (PF-05082566) targets this receptor to stimulate a more intense immune system attack on cancers.<ref name=Pfizer2016-05>[https://www.reuters.com/article/us-health-cancer-pfizer-immunotherapy-idUSKCN0Y92W2 Pfizer cancer drug shows promise in combo with Merck's Keytruda. May 2016]</ref> It is a fully human IgG2 monoclonal antibody.<ref>[http://www.ercongressi.it/slides-NDH-Carlton/10-05/A-Thall.pdf Phase 1 Study of Utomilumab (PF-05082566) In Combination with Rituximab in Patients with CD20+ NHL (Study B1641001)]</ref> It is in early clinical trials.<ref name=Pfizer2016-05/> {{as of |2016|6}} 5 clinical trials are active.<ref>[https://clinicaltrials.gov/ct2/results?term=PF-05082566&Search=Search PF-05082566 trials]</ref>
 
== See also ==
* [[4-1BB ligand]]
* [[4-1BB ligand]]
* [[Urelumab]]


== References ==
== References ==
* {{cite journal |author=Kwon BS, Weissman SM |title=cDNA sequences of two inducible T-cell genes |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=86 |issue=6 |pages=1963-7 |year=1989 |pmid=2784565 |doi=}}
{{Reflist}}
 
==External links==
* {{UCSC gene info|TNFRSF9}}


* {{cite journal |author=Schwarz H, Tuckwell J, Lotz M |title=A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family |journal=Gene |volume=134 |issue=2 |pages=295-8 |year=1993 |pmid=8262389 |doi=}}
== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Kwon BS, Weissman SM | title = cDNA sequences of two inducible T-cell genes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 86 | issue = 6 | pages = 1963–7 | year = 1989 | pmid = 2784565 | pmc = 286825 | doi = 10.1073/pnas.86.6.1963 }}
* {{cite journal | vauthors = Schwarz H, Tuckwell J, Lotz M | title = A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family | journal = Gene | volume = 134 | issue = 2 | pages = 295–8 | year = 1993 | pmid = 8262389 | doi = 10.1016/0378-1119(93)90110-O }}
* {{cite journal | vauthors = Sica G, Chen L | title = Biochemical and immunological characteristics of 4-1BB (CD137) receptor and ligand and potential applications in cancer therapy | journal = Arch. Immunol. Ther. Exp. (Warsz.) | volume = 47 | issue = 5 | pages = 275–9 | year = 2000 | pmid = 10604232 | doi =  }}
* {{cite journal | vauthors = Schwarz H | title = Biological activities of reverse signal transduction through CD137 ligand | journal = J. Leukoc. Biol. | volume = 77 | issue = 3 | pages = 281–6 | year = 2005 | pmid = 15618293 | doi = 10.1189/jlb.0904558 }}
* {{cite journal | vauthors = Kwon BS, Weissman SM | title = cDNA sequences of two inducible T-cell genes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 86 | issue = 6 | pages = 1963–7 | year = 1989 | pmid = 2784565 | pmc = 286825 | doi = 10.1073/pnas.86.6.1963 }}
* {{cite journal | vauthors = Zhou Z, Kim S, Hurtado J, Lee ZH, Kim KK, Pollok KE, Kwon BS | title = Characterization of human homologue of 4-1BB and its ligand | journal = Immunol. Lett. | volume = 45 | issue = 1–2 | pages = 67–73 | year = 1995 | pmid = 7622190 | doi = 10.1016/0165-2478(94)00227-I }}
* {{cite journal | vauthors = Alderson MR, Smith CA, Tough TW, Davis-Smith T, Armitage RJ, Falk B, Roux E, Baker E, Sutherland GR, Din WS | title = Molecular and biological characterization of human 4-1BB and its ligand | journal = Eur. J. Immunol. | volume = 24 | issue = 9 | pages = 2219–27 | year = 1994 | pmid = 8088337 | doi = 10.1002/eji.1830240943 }}
* {{cite journal | vauthors = Schwarz H, Tuckwell J, Lotz M | title = A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family | journal = Gene | volume = 134 | issue = 2 | pages = 295–8 | year = 1994 | pmid = 8262389 | doi = 10.1016/0378-1119(93)90110-O }}
* {{cite journal | vauthors = Schwarz H, Blanco FJ, von Kempis J, Valbracht J, Lotz M | title = ILA, a member of the human nerve growth factor/tumor necrosis factor receptor family, regulates T-lymphocyte proliferation and survival | journal = Blood | volume = 87 | issue = 7 | pages = 2839–45 | year = 1996 | pmid = 8639902 | doi =  }}
* {{cite journal | vauthors = Loo DT, Chalupny NJ, Bajorath J, Shuford WW, Mittler RS, Aruffo A | title = Analysis of 4-1BBL and laminin binding to murine 4-1BB, a member of the tumor necrosis factor receptor superfamily, and comparison with human 4-1BB | journal = J. Biol. Chem. | volume = 272 | issue = 10 | pages = 6448–56 | year = 1997 | pmid = 9045669 | doi = 10.1074/jbc.272.10.6448 }}
* {{cite journal | vauthors = Schwarz H, Arden K, Lotz M | title = CD137, a member of the tumor necrosis factor receptor family, is located on chromosome 1p36, in a cluster of related genes, and colocalizes with several malignancies | journal = Biochem. Biophys. Res. Commun. | volume = 235 | issue = 3 | pages = 699–703 | year = 1997 | pmid = 9207223 | doi = 10.1006/bbrc.1997.6870 }}
* {{cite journal | vauthors = Arch RH, Thompson CB | title = 4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB | journal = Mol. Cell. Biol. | volume = 18 | issue = 1 | pages = 558–65 | year = 1998 | pmid = 9418902 | pmc = 121523 | doi =  }}
* {{cite journal | vauthors = Jang IK, Lee ZH, Kim YJ, Kim SH, Kwon BS | title = Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B | journal = Biochem. Biophys. Res. Commun. | volume = 242 | issue = 3 | pages = 613–20 | year = 1998 | pmid = 9464265 | doi = 10.1006/bbrc.1997.8016 }}
* {{cite journal | vauthors = Kim YJ, Kim SH, Mantel P, Kwon BS | title = Human 4-1BB regulates CD28 co-stimulation to promote Th1 cell responses | journal = Eur. J. Immunol. | volume = 28 | issue = 3 | pages = 881–90 | year = 1998 | pmid = 9541583 | doi = 10.1002/(SICI)1521-4141(199803)28:03<881::AID-IMMU881>3.0.CO;2-0 }}
* {{cite journal | vauthors = Saoulli K, Lee SY, Cannons JL, Yeh WC, Santana A, Goldstein MD, Bangia N, DeBenedette MA, Mak TW, Choi Y, Watts TH | title = CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand | journal = J. Exp. Med. | volume = 187 | issue = 11 | pages = 1849–62 | year = 1998 | pmid = 9607925 | pmc = 2212301 | doi = 10.1084/jem.187.11.1849 }}
* {{cite journal | vauthors = Langstein J, Michel J, Schwarz H | title = CD137 induces proliferation and endomitosis in monocytes | journal = Blood | volume = 94 | issue = 9 | pages = 3161–8 | year = 1999 | pmid = 10556203 | doi =  }}
* {{cite journal | vauthors = Jang LK, Lee ZH, Kim HH, Hill JM, Kim JD, Kwon BS | title = A novel leucine-rich repeat protein (LRR-1): potential involvement in 4-1BB-mediated signal transduction | journal = Mol. Cells | volume = 12 | issue = 3 | pages = 304–12 | year = 2002 | pmid = 11804328 | doi =  }}
* {{cite journal | vauthors = Cooper D, Bansal-Pakala P, Croft M | title = 4-1BB (CD137) controls the clonal expansion and survival of CD8 T cells in vivo but does not contribute to the development of cytotoxicity | journal = Eur. J. Immunol. | volume = 32 | issue = 2 | pages = 521–9 | year = 2002 | pmid = 11828369 | doi = 10.1002/1521-4141(200202)32:2<521::AID-IMMU521>3.0.CO;2-X }}
* {{cite journal | vauthors = Wilcox RA, Chapoval AI, Gorski KS, Otsuji M, Shin T, Flies DB, Tamada K, Mittler RS, Tsuchiya H, Pardoll DM, Chen L | title = Cutting edge: Expression of functional CD137 receptor by dendritic cells | journal = J. Immunol. | volume = 168 | issue = 9 | pages = 4262–7 | year = 2002 | pmid = 11970964 | doi = 10.4049/jimmunol.168.9.4262 }}
* {{cite journal | vauthors = Shulzhenko N, Morgun A, Chinellato AP, Rampim GF, Diniz RV, Almeida DR, Gerbase-DeLima M | title = CD27 but not CD70 and 4-1BB intragraft gene expression is a risk factor for acute cardiac allograft rejection in humans | journal = Transplant. Proc. | volume = 34 | issue = 2 | pages = 474–5 | year = 2002 | pmid = 12009595 | doi = 10.1016/S0041-1345(02)02600-3 }}
* {{cite journal | vauthors = Pauly S, Broll K, Wittmann M, Giegerich G, Schwarz H | title = CD137 is expressed by follicular dendritic cells and costimulates B lymphocyte activation in germinal centers | journal = J. Leukoc. Biol. | volume = 72 | issue = 1 | pages = 35–42 | year = 2002 | pmid = 12101260 | doi =  }}
{{refend}}


{{Clusters of differentiation }}
{{Clusters of differentiation }}
{{Tumor necrosis factor receptor superfamily}}
{{Tumor necrosis factor receptor superfamily}}
{{Cytokine receptor modulators}}
{{DEFAULTSORT:Cd137}}


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Latest revision as of 07:09, 2 July 2017

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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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CD137 is a member of the tumor necrosis factor (TNF) receptor family. Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB and induced by lymphocyte activation (ILA). It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule.

Expression

CD137 can be expressed by activated T cells, but to a larger extent on CD8 than on CD4 T cells. In addition, CD137 expression is found on dendritic cells, B cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of inflammation.

Specific effects on cells

The best characterized activity of CD137 is its costimulatory activity for activated T cells. Crosslinking of CD137 enhances T cell proliferation, IL-2 secretion, survival and cytolytic activity. Further, it can enhance immune activity to eliminate tumors in mice.

Interactions

CD137 has been shown to interact with TRAF2.[1][2]

As a drug target

Utomilumab

Utomilumab (PF-05082566) targets this receptor to stimulate a more intense immune system attack on cancers.[3] It is a fully human IgG2 monoclonal antibody.[4] It is in early clinical trials.[3] As of June 2016 5 clinical trials are active.[5]

See also

References

  1. ↑ Jang IK, Lee ZH, Kim YJ, Kim SH, Kwon BS (Jan 1998). "Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B". Biochem. Biophys. Res. Commun. 242 (3): 613–20. doi:10.1006/bbrc.1997.8016. PMID 9464265.
  2. ↑ Arch RH, Thompson CB (Jan 1998). "4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB". Mol. Cell. Biol. 18 (1): 558–65. PMC 121523. PMID 9418902.
  3. ↑ 3.0 3.1 Pfizer cancer drug shows promise in combo with Merck's Keytruda. May 2016
  4. ↑ Phase 1 Study of Utomilumab (PF-05082566) In Combination with Rituximab in Patients with CD20+ NHL (Study B1641001)
  5. ↑ PF-05082566 trials

External links

Further reading

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