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| Antibodies from IMGENEX: TNF Family & Death Receptors |
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The tumor necrosis factor (TNF) was originally
identified as a protein that kills tumor cells. Research during the past two
decades has shown the existence of a superfamily of TNF proteins consisting of
19 members that signal through 29 receptors. The members of the TNF super family
exhibit 15-25% amino acid sequence homology with each other and bind to distinct
receptors, which are homologous in their extracellular domain. The cytokines
belonging to TNF family includes TNFa, TNFb, BLys/BAFF, OPGL/TRANCE/RANKL,
APRIL, TRAIL, FasL,
etc.Members of the TNF receptor superfamily play pivotal roles in numerous
biological events in metazoan organisms. Ligand-mediated trimerization by
corresponding homo- or hetero-trimeric ligands, the TNF family proteins, causes
recruitment of several intracellular adaptors, which activate multiple signal
transduction pathways. Based upon their cytoplasmic sequences and signaling
properties, these TNF receptors can be classified into three major groups
(Ref.1). The first group, including Fas/ CD95/ Apo1/ APT1,
TNFR1/CD120a/p55-R/TNFAR/TNFR60, DR3/ TRAMP/
WSL1/ LARD /WSLLR/DDR3/TR3/Apo3, DR4/TRAILR1/Apo2,
DR5/TRAILR2/KILLER/TRICK2A/TRICKB,
and DR6/TR7,
contains a DD (Death Domain) in the cytoplasmic tail. Fas, DR4 and DR5 interact
with the FADD (Fas-Associated Death Domain) while TNFR1 and DR3 interact with
the adaptor TRADD
(TNFR-Associated Death Domain). These molecules, in turn cause activation of the
Caspase
cascade and induction of apoptosis (Ref.2).
The second group includes
TNFR2/p75/CD120b/TNFR80/TNFBR, CD40/p50/Bp50, CD30/Ki-1/D1S166E, CD27/Tp55/S152,
TNFR2-RP/TNFCR/TNFRIII, LT-BetaR, OX40/ CD134/ACT35/TXGP1L, 4-1BB/CD137/ILA,
BAFFR, BCMA/BCM, TACI/CAML
interactor, RANK/TRANCE-R,
p75NGFR, HVEM (Herpes Virus Entry Mediator)/HveA/ATAR/TR2/ LIGHTR, GITR/AITR/
TNFRSF18, TROY/TAJ,
EDAR, XEDAR/EDA-A2R, RELT and Fn14/TWEAKR. These receptors contain one or more
TIM (TRAF Interacting Motifs) in their cytoplasmic tails. Activation of TIM
containing TNF receptors lead to recruitment of TRAF family members, and
activation of multiple signal transduction pathways such as NF-KappaB (Nuclear
Factor-KappaB), JNK (Jun N-terminal Kinase), p38, ERK (Extracellular Signal
Regulated Kinase) and PI3K (Phosphoinisitide-3 Kinase) (Ref.3). The third group
of TNF receptor family members, including DcR1/TRID/TRAIL-R3, DcR2/
TRUNDD/TRAIL-R4, DcR3 and OPG, does not contain functional intracellular
signaling domains or motifs. Although this group of receptors cannot provide
intracellular signaling, they can effectively compete with the other two
signaling groups of receptors for their corresponding ligands. These DcR (Decoy
Receptors) therefore function by impeding the activation of signal transduction
pathways by other TNF receptors (Ref.4).
A key component of signaling by
members of the tumor necrosis factor receptor (TNF-R) family is interaction with
the cytoplasmic adapter proteins known as TRAFs (TNF
receptor associate factors). TRAFs are a major group of intracellular adaptors
that bind directly or indirectly to many members of the TNF receptor
superfamily. Six mammalian TRAFs, TRAF1, TRAF2, TRAF3,
TRAF4, TRAF5 and TRAF6, have
been identified. TRAFs can induce the activation of several kinase cascades that
ultimately lead to the activation of signal transduction pathways such as
NF-KappaB, JNK, ERK, p38 and
PI3K, which can regulate cellular processes ranging from cell proliferation and
differentiation to apoptosis. Other proteins, which are involved in TNF
signaling, are DRAKs (Death Receptor Kinase 1 and 2), SODD
(Silencer of Death domain), ARTs,
etc.
All the cytokines of the TNF superfamily mediate their effects
through the activation of the transcription factor NF-kappaB, c-Jun N-terminal
kinase, apoptosis, and proliferation. Thus, agents that can either suppress the
production of these cytokines or block their action have therapeutic value for a
wide variety of diseases. Indeed, a number of biologic TNF blocking therapies
are being used now to inhibit the inflammation associated with Crohn’s disease
and rheumatoid arthritis Thus, the continued examination of TNFR signal
transduction will provide the tools for receptor or tissue specific
interventions, allowing more targeted treatments that have fewer side
effects. |
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| References: |
1. Dempsey PW, Doyle SE, He JQ, Cheng G.
The signaling adaptors
and pathways activated by TNF superfamily.
Cytokine Growth Factor Rev. 2003
Jun-Aug;14(3-4):193-209.
PMID: 12787559
2. Kischkel FC, Lawrence DA,
Chuntharapai A, Schow P, Kim KJ, Ashkenazi A.
Apo2L/TRAIL-dependent
recruitment of endogenous FADD and caspase-8 to death receptors 4 and
5.
Immunity. 2000 Jun;12(6):611-20.
PMID: 10894161
3. Darnay BG,
Ni J, Moore PA, Aggarwal BB.Activation of NF-kappaB by RANK requires tumor
necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing
kinase. Identification of a novel TRAF6 interaction motif.
J Biol Chem. 1999
Mar 19;274(12):7724-31.
PMID: 10075662
4. Gibson SB, Oyer R, Spalding
AC, Anderson SM, Johnson GL.
Increased expression of death receptors 4 and 5
synergizes the apoptosis response to combined treatment with etoposide and
TRAIL.
Mol Cell Biol. 2000 Jan;20(1):205-12.
PMID: 10594023 |
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| Primary
search |
|
Fas, CD95, APO1, APT1, FasL, Fas Ligand,
TNFR1, Tumor Necrosis Factor Receptor-1, CD120a, p55R, TNFAR, TNFR60, DR3, Death
Receptor-3, TRAMP, WSL1, LARD, Lymphocyte-Associated Receptor of Death,
WSLLR, DDR3, TR3, Apo3, DR4, Death Receptor-4, TRAILR1, TNF-Related
Apoptosis-Inducing Ligand Receptor-1, Apo2, DR5, Death Receptor-5, TRAILR2,
KILLER, TRICK2A, TRICKB, DR6, Death
Receptor-6, TR7, DD, Death Domain, TNFR2, Tumor Necrosis Factor
Receptor-2, p75, CD120b, TNFR80, TNFBR, CD40, p50, Bp50, CD30, Ki-1, D1S166E,
CD27, Tp55, S152, LT-BetaR, TNFR2- RP, TNFCR, TNFRIII, OX40, CD134, ACT35,
TXGP1L, 4-1BB, CD137, ILA, Induced by Lymphocyte Activation, BAFFR, B-cell
Activation Factor Receptor, BCMA, B-Cell Maturation Antigen, BCM, TACI,
Transmembrane Activator and Calcium Modulator Cyclophilin Ligand Interaction,
CAML interactor, RANK, TRANCER, NGFR, Nerve Growth Factor Receptor, HVEM, Herpes
Virus Entry Mediator, HveA, ATAR, TR2, LIGHTR, GITR,
Glucocorticoid-Induced TNFR-Related Gene, AITR, Activation-Inducible TNFR
Family Member, TNFRSF18, TROY,TAJ, EDAR, Ectodysplasin-1, Anhidrotic Receptor,
XEDAR, EDA-A2R, RELT, Fn14, DcR1,Decoy Receptor-1, TRID, TRAILR3, DcR2, Decoy
Receptor-2, TRUNDD, TRAILR4, DcR3, Decoy Receptor-3, Opg, Osteoprotegerin,
TRAFs, TNF Receptor-Associated Factors, NF-KappaB, Nuclear Factor-KappaB,
JNK, Jun N-terminal Kinase, ERK, Extracellular Signal Regulated Kinase,
p38, PI3K, Phosphoinisitide-3 Kinase, FADD, Fas Associated Death Domain, TRADD,
TNFR-Associated Death Domain protein, Caspases, TIM, TRAF Interacting
Motifs, Apoptosis, Gene Expression, CD40L, CD30L, CD27L, 4-1BBL, LT-Beta, OX40L,
APRIL, RANKL, NGF. |
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| Secondary search |
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TAK,
TGF-Beta-Activating Kinase, TAB, TAK Binding Protein, MEKs, Akt, PKB,
Protein Kinase-B, TNF-Alpha, TNF-Beta, Tumour Necrosis Factor-Alpha, Tumour
Necrosis Factor-Beta, GITRL, EDA1, EDA2, I-KappaB, Inhibitor of Kappa Light
Chain Gene Enhancer in B-Cells, I-KappaB-Alpha, I-KappaB-Beta, I-KappaB-Epsilon,
Caspase1, Caspase2, Caspase3, Caspase4, Caspase5, Caspase6, Caspase7, Caspase8,
Caspase9, Caspase10, I-KappaB Kinase, IKK-Alpha, IKK-Beta, IKK- Epsilon,
IKK-Gamma, TRAF1, TNF Receptor-Associated Factor-1, TRAF2, TRAF3, TRAF4, TRAF5,
TRAF6. |
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| Category Apoptosis,
Cell Signaling, Cytokines, Disease Pathway, Immunology, Stress Activated
Pathway. |
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| Found 66 results | Show all |
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Format |
Species |
Clone |
Application |
Quantity |
Price |
MSDS |
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| IMG-247 |
BLyS/BAFF/THANK/TALL-1 |
Purified |
H, M |
N/A |
WB |
0.1 mg |
241 |
 |
 |
| IMG-6542A |
CD27 |
Purified |
H |
203.6 |
Flow (Cell Surface), IF/ICC, IHC (frozen) |
0.1 mg |
236 |
|
|
| IMG-112-1 |
DAXX |
Purified |
H |
N/A |
WB |
0.05 mg |
321 |
|
|
| IMG-112-2 |
DAXX |
Purified |
H |
N/A |
WB |
0.1 mg |
401 |
|
|
| IMG-245-1 |
DcR1 |
Purified |
H |
N/A |
WB |
0.05 mg |
321 |
|
|
| IMG-245-2 |
DcR1 |
Purified |
H |
N/A |
WB |
0.1 mg |
401 |
|
|
| IMG-121-1 |
DcR2 |
Purified |
H |
N/A |
Flow (Cell Surface), WB |
0.05 mg |
321 |
|
|
| IMG-121-2 |
DcR2 |
Purified |
H |
N/A |
Flow (Cell Surface), WB |
0.1 mg |
401 |
|
|
| IMG-143 |
DcR3 |
Purified |
H |
37A565 |
WB |
0.1 mg |
263 |
|
|
| IMG-5024 |
DR3 |
Purified |
H |
N/A |
WB |
0.1 mg |
229 |
|
|
| IMG-106-1 |
DR3 (NT) |
Purified |
H |
N/A |
WB |
0.05 mg |
321 |
|
|
| IMG-106-2 |
DR3 (NT) |
Purified |
H |
N/A |
WB |
0.1 mg |
401 |
|
|
| IMG-275 |
DR4/TRAILR1 |
Purified |
H, M, R |
32A242 |
WB |
0.1 mg |
263 |
|
|
| IMG-141A |
DR4/TRAILR1 |
Purified |
H |
32A1380 |
FA (Neutralization), Flow (Cell Surface), WB |
0.1 mg |
263 |
|
|
| IMG-108-1 |
DR4/TRAILR1 (CT) |
Purified |
H |
N/A |
WB |
0.05 mg |
321 |
|
|
| IMG-108-2 |
DR4/TRAILR1 (CT) |
Purified |
H |
N/A |
WB |
0.1 mg |
401 |
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| IMG-109-1 |
DR4/TRAILR1 (NT) |
Purified |
H |
N/A |
WB |
0.05 mg |
321 |
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|
| IMG-109-2 |
DR4/TRAILR1 (NT) |
Purified |
H |
N/A |
WB |
0.1 mg |
401 |
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| IMG-120A |
DR5/TRAILR2 |
Purified |
H |
N/A |
Flow (Cell Surface), IF/ICC, IHC (paraffin), WB |
0.1 mg |
252 |
|
|
| IMG-120E |
DR5/TRAILR2 |
Azide-Free |
H |
N/A |
Flow (Cell Surface), IF/ICC, IHC (paraffin), WB |
0.1 mg |
287 |
|
|
| IMG-166 |
DR6 |
Purified |
H |
N/A |
WB |
0.1 mg |
229 |
|
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| IMG-5604-1 |
DR6 |
Purified |
H |
N/A |
WB |
0.05 mg |
321 |
|
|
| IMG-5604-2 |
DR6 |
Purified |
H |
N/A |
WB |
0.1 mg |
401 |
|
|
| IMG-157-1 |
DRAK1 |
Purified |
H |
N/A |
WB |
0.05 mg |
321 |
|
|
| IMG-157-2 |
DRAK1 |
Purified |
H |
N/A |
WB |
0.1 mg |
401 |
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| IMG-151A |
DRAK2 |
Purified |
H |
N/A |
WB |
0.1 mg |
241 |
|
|
| IMG-80403 |
Fas (CD95) |
Purified |
H |
N/A |
IHC (paraffin) |
0.5 mL |
371 |
 |
|
| IMG-103A |
OPG |
Purified |
H |
98A1071 |
IHC (paraffin), WB |
0.1 mg |
269 |
|
|
| IMG-454 |
PHAPI2/APRIL |
Purified |
H |
N/A |
WB |
0.1 mg |
241 |
|
|
| IMG-3547 |
PHAPI2/APRIL |
Purified, Peptide Affinity |
H |
N/A |
WB |
0.1 mg |
333 |
|
|
| IMG-485 |
Punctin |
Ascites |
H, M, R |
30D445.1 |
WB |
0.2 mL |
263 |
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| IMG-128A |
RANK |
Purified |
H, M |
9A725 |
Flow (Intracellular), IHC (paraffin), WB |
0.1 mg |
252 |
|
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| IMG-5116A |
RANK/TNF11aR/ODFR |
Purified |
H, M |
N/A |
WB |
0.1 mg |
241 |
|
|
| IMG-325A |
RANK/TNF11aR/ODFR |
Purified |
H, M |
64C1385.1 |
IP, WB |
0.1 mg |
281 |
|
|
| IMG-325D |
RANK/TNF11aR/ODFR |
PE |
H, M |
64C1385.1 |
Flow (Cell Surface) |
0.1 mg |
354 |
|
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| IMG-185A |
RANKL/TRANCE/CD254 |
Purified |
H, M |
12A380 |
Flow (Cell Surface), IHC (frozen), WB |
0.1 mg |
281 |
|
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| IMG-5090A |
RANKL/TRANCE/CD254 |
Purified |
M |
N/A |
WB |
0.1 mg |
246 |
|
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| IMG-152 |
SODD |
Purified |
H |
N/A |
Flow (Cell Surface), WB |
0.1 mg |
229 |
|
|
| IMG-5818A |
SODD |
Purified |
Bo, D, H, M, R, RH |
N/A |
WB |
0.1 mg |
229 |
|
|
| IMG-5829-1 |
SODD |
Purified |
H, M, R |
N/A |
WB |
0.05 mg |
321 |
|
|
| IMG-5829-2 |
SODD |
Purified |
H, M, R |
N/A |
WB |
0.1 mg |
401 |
|
|
| IMG-280 |
STAT1a/b |
Purified |
Chp, D, H, M, Pi |
N/A |
WB |
0.1 mg |
241 |
|
|
| IMG-291 |
STAT2 |
Purified |
H |
N/A |
WB |
0.1 mg |
229 |
|
|
| IMG-461 |
STAT4 |
Purified |
M, R |
N/A |
WB |
0.2 mL |
220 |
|
|
| IMG-292 |
STAT5b |
Purified |
H |
N/A |
WB |
0.1 mg |
241 |
|
|
| IMG-462 |
STAT6 |
Purified |
H |
N/A |
WB |
0.2 mL |
220 |
|
|
| IMX-5057 |
STAT6 |
Sera |
H, M, R |
N/A |
Peptide ELISA |
0.1 mL |
185 |
|
|
| IMG-6249A |
STAT6 |
Purified |
H, M, R |
N/A |
IF/ICC, WB |
0.1 mg |
252 |
|
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| IMG-408A |
STAT6 (Tyr641) |
Purified |
H, M |
177C322 |
IP, WB |
0.1 mg |
274 |
|
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| IMG-176-1 |
TACE |
Purified |
H, M, R |
N/A |
WB |
0.05 mg |
321 |
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