"Prosci"

Supplier: Prosci

ST2 Antibody: ST2 is a member of a superfamily containing the interleukin-1 receptor and the Toll-like receptors (TLRs). The TLRs are signaling molecules that recognize different microbial products during infection and serve as an important link between the innate and adaptive immune responses. ST2 was originally identified as a protein whose production was stimulated by various proliferation-inducing agents such as PDGF and FGF. More recently, it has been shown to negatively regulate IL-1 receptor and Toll-like receptor (TLR) 4 signaling and to maintain endotoxin tolerance. It has been suggested that the inhibition of TLR4 signaling occurs through the association and sequestering of TLR adaptor molecules such as MyD88 and TIRAP.

Supplier: Prosci

SIGIRR Antibody: SIGIRR is a member of the Toll-like receptor-interleukin 1 receptor superfamily. Members of this family are defined by the presence of an intracellular Toll-IL-1R (TIR) domain. The Toll-like receptors (TLRs) are signaling molecules that recognize different microbial products during infection and serve as an important link between the innate and adaptive immune responses. SIGIRR was originally identified through database analysis and was shown to have only one Ig domain as opposed to the normal three Ig folds seen in the TIR family. Similar to ST2, another TIR family member, it has been shown to negatively regulate IL-1 receptor and Toll-like receptor signaling. However, SIGIRR inhibits TLR-IL-1R signaling by dimerizing with TLR4, TLR5, TLR9, and IL-1R. It also associates with the down-stream TLR signaling proteins IRAK and TRAF6 in an IL-1-dependent fashion.

Supplier: Prosci

TRIAD3A Antibody: Activation of NF-kappa B as a result of Toll-like receptor (TLR) and IL-1 receptor signaling is a major component of innate immune responses. Signals from these receptors are relayed by a number of adapter molecules such as TRIF, TIRAP, and MyD88. Several regulatory mechanisms exist to control TLR signal transduction, including the inhibition of TLR expression and signaling by molecules such as ST2 and SIGIRR. Another mechanism is by the ubi-quitinization of selected TLRs by TRIAD3A, an E3 ubiquitin-protein ligase. TRIAD3A is a RING finger protein that can bind to TLR4 and TLR9, and to a lesser extent TLR3 and TLR5, catalyzing the ubiquitization of these molecules. Overexpression of TRIAD3A promoted the nearly complete degradation of TLR4 and TLR9; this reduction was reflected in the decreased signal-specific activation by ligands specific for these TLRs. Conversely, depletion of TRIAD3A resulted in enhanced TLR activation.

Supplier: Prosci

UBC13 Antibody: Ubiquitin-conjugating enzyme 13 (Ubc13) was initially discovered in S. cerevisiae as a DNA-damage inducible protein involved in the error-free DNA postreplication repair pathway. It has recently been shown to be an important component of the Toll-like receptor and IL-1R signaling pathway. Signals from these pathways are relayed by a number of downstream molecules such as MyD88 and tumor necrosis factor receptor associated factor (TRAF6), ultimately activating various kinases and transcription factors. Ubc13 is part of a dimeric ubiquitin-conjugating enzyme complex also containing UEV1A (ubiquitin-conjugating enzyme E2 variant 1) that together with TRAF6 activates TAK1, a member of the mitogen-activated protein kinase kinase kinase family. The Ubc13-UEV1A complex also mediates the Lys-63 ubiquitination of TRAF-6, and this ubiquitination is essential for TAK1 activation.

Supplier: Prosci

UEV1A Antibody: Ubiquitin-conjugating enzyme E2 (UEV1) was initially discovered as a protein similar in sequence and structure to the E2 ubiquitin-conjugating enzymes but lacking their enzymatic activity. There are at least two variants and multiple isoforms of UEV1. In particular, UEV1A (Ubiquitin-conjugating enzyme E2 variant 1 isoform A) has recently been shown to be an important component of the Toll-like receptor and IL-1R signaling pathway. Signals from these pathways are relayed by a number of downstream molecules such as MyD88 and tumor necrosis factor receptor associated factor (TRAF6), ultimately activating various kinases and transcription factors. UEV1A is part of a dimeric ubiquitin-conjugating enzyme complex also containing Ubc13 (ubiquitin-conjugating enzyme 13) that together with TRAF6 activates TAK1, a member of the mitogen-activated protein kinase kinase kinase family. The Ubc13-UEV1A complex also mediates the Lys-63 ubiquitination of TRAF-6, and this ubiquitination is essential for TAK1 activation.

Supplier: Prosci

ECSIT Antibody: Activation of NF-kappa B as a result of Toll-like receptor (TLR) and IL-1 receptor signaling is a major component of innate immune responses. Signals from these receptors are relayed by a number of adapter molecules such as TRIF, TIRAP, and MyD88 to kinases such as IRAK and other intermediates such as TNF receptor associated factor (TRAF)-6. ECSIT (evolutionarily conserved signaling intermediate in Toll pathways) was initially identified as a cytoplasmic protein interacting specifically with TNF receptor associated factor (TRAF)-6 in the TLR pathway. Recently however, ECSIT has also been shown to be required for bone morphogenetic protein (Bmp) signaling and mesoderm formation during mouse embryogenesis, indicating the possibility of cross-talk between the TLR/IL-B and Bmp signaling pathways.

Supplier: Prosci

TAK1 Antibody: TAK1 (TGF-beta activated protein kinase 1) is a widely expressed enzyme originally identified as a mitogen-activated protein kinase kinase kinase (MAP3K7). It has since been shown to mediate various intracellular signaling pathways, such as those induced by TGF-beta and members of the Toll-IL-1R (TIR) superfamily, thus acting as an intermediate in both proliferative and innate and adaptive immune responses. TAK1 is normally present in cells in a complex with TAK1-binding protein 1 (TAB1) and either TAB2 or TAB3. Association with TAB1 triggers TAK1 kinase activity by inducing TAK1 autophosphorylation, while TAB2 and possibly TAB3 may contribute to SAPK2a/p38a-mediated feedback inhibition of TAK1 activity.

Supplier: Prosci

TAB1 Antibody: TAB1 was identified as a regulator of the MAP kinase kinase kinase TAK1/MAP3K7, which is known to mediate various intracellular signaling pathways, such as those induced by TGF-beta and members of the Toll-IL-1R (TIR) superfamily, thus acting as an intermediate in both proliferative and innate and adaptive immune responses. This protein, together with either TAB2 or TAB3, activates TAK1 kinase in response to upstream signals. It has been shown that the C-terminal portion of TAB1 is sufficient for binding and activation of TAK1, while a portion of the N-terminus acts as a dominant-negative inhibitor of TGF-beta, demonstrating how this protein can function as a mediator between TGF-beta receptors and TAK1.

Supplier: Prosci

TAB2 Antibody: TAB2 is an activator of MAP3K7/TAK1, which is required for for the IL-1 induced activation NF-kappaB and MAPK8/JNK. This protein forms a kinase complex with TRAF6, MAP3K7 and TAB1, thus serves as an adaptor linking MAP3K7 and TRAF6. This protein, TAB1, and MAP3K7 also participate in the signal transduction induced by TNFSF11/RANKL through the activation of the receptor activator of NF-kappaB (TNFRSF11A/RANK), which may regulate the development and function of osteoclasts. Recent experiments have shown that TAB2 and the related protein TAB3 constitutitvely interact with the autophagy mediator Beclin-1; upon induction of autophagy, these proteins dissociate from Beclin-1 and bind TAK1. Overexpression of TAB2 and TAB3 inhibit autophagy, while their depletion triggers it, suggesting that TAB2 and TAB3 act as a control point for autophagy.

Supplier: Prosci

TAB3 Antibody: TAB3 functions in the NF-kappaB signal transduction pathway. It and the similar and functionally redundant protein TAB2, form a ternary complex with the protein kinase TAK1 and either TRAF2 or TRAF6 in response to stimulation with the pro-inflammatory cytokines TNF or IL-1. Subsequent TAK1 kinase activity triggers a signaling cascade leading to activation of the NF-kappaB transcription factor. Recent experiments have shown that TAB2 and the related protein TAB3 constitutitvely interact with the autophagy mediator Beclin-1; upon induction of autophagy, these proteins dissociate from Beclin-1 and bind TAK1. Overexpression of TAB2 and TAB3 inhibit autophagy, while their depletion triggers it, suggesting that TAB2 and TAB3 act as a control point for autophagy.

Supplier: Prosci

BTK Antibody: Bruton's tyrosine kinase (BTK) was initially identified as a member of the src family for protein-tyrosine kinases that was involved in X-linked agamma-globulinaemia, and has since been shown to involved in a number of signaling pathways in hemapoietic lineage. It has recently been shown to interact with members of the toll-like receptor (TLR) family such as TLR4, 6, 8, and 9. The TLRs are critical molecules in both the innate and adaptive immunity and can recognize diverse microbial pathogens. BTK has also been shown to interact with key proteins involved in TLR4 signal transduction such as MyD88, TIRAP, and IRAK, but not TRAF-6, suggesting that BTK is involved in lipopolysaccharide signal transduction.

Supplier: Prosci

IRF3 Antibody: Interferons (IFN)s are involved in a multitude of immune interactions during viral infections and play a major role in both the induction and regulation of innate and adaptive antiviral mechanisms. During infection, host-virus interactions signal downstream molecules such as transcription factors such as IFN regulatory factor-3 (IRF3) which can act to stimulate transcription of IFN-alpha/beta genes. IRF3 is present in an inactive form in the cytoplasm of most cells. Following viral infection, IRF3 can be activated by I kappa B kinase- epsilon and TANK-binding kinase 1 (TBK1), whereupon IRF3 translocates to the nucleus. IRF3 can also be activated by stimulation of toll-like receptor 3 (TLR3) by dsRNA. IRF3 exists as at least two distinct isoforms.

Supplier: Prosci

IRF3 Antibody: Interferons (IFN)s are involved in a multitude of immune interactions during viral infections and play a major role in both the induction and regulation of innate and adaptive antiviral mechanisms. During infection, host-virus interactions signal downstream molecules such as transcription factors such as IFN regulatory factor-3 (IRF3) which can act to stimulate transcription of IFN-alpha/beta genes. IRF3 is present in an inactive form in the cytoplasm of most cells. Following viral infection, IRF3 can be activated by I kappa B kinase- epsilon and TANK-binding kinase 1 (TBK1), whereupon IRF3 translocates to the nucleus. IRF3 can also be activated by stimulation of toll-like receptor 3 (TLR3) by dsRNA. IRF3 exists as at least two distinct isoforms.

Supplier: Prosci

IRF8 Antibody: Interferons (IFN)s are involved in a multitude of immune interactions during viral infections and play a major role in both the induction and regulation of innate and adaptive antiviral mechanisms. During infection, host-virus interactions signal downstream molecules such as transcription factors such as IFN regulatory factor-3 (IRF3) which can act to stimulate transcription of IFN-alpha/beta genes. Unlike IRF3, IRF8 appears to act as a negative regulator of IFN-induced genes in most cases, but IRF8 mediates activation of NF-kappa B by the toll-like receptor 9 (TLR9) after stimulation by unmethylated CpG DNA in dendritic cells. Finally, it has been shown that IRF8 decreases bcl-2 expression and thus may play a role in chronic myelogenous leukemia.

Supplier: Prosci

Bim Antibody: Members in the Bcl-2 family are critical regulators of apoptosis by either inhibiting or promoting cell death. Bcl-2 homology 3 (BH3) domain is a potent death domain. BH3 domain containing pro-apoptotic proteins, including Bad, Bax, Bid, Bik, and Hrk, form a growing subclass of the Bcl-2 family. A novel BH3 domain containing protein was recently identified and designated Bim or BOD in human, mouse and rat. Bim/BOD interacts with diverse members in the pro-survival Bcl-2 sub-family including Bcl-2, Bcl-xL and Bcl-w. Bim/BOD induces apoptosis. The messenger RNA of Bim is ubiquitously expressed in multiple tissues and cell lines.

Supplier: Prosci

XAF-1 Antibody: XAF-1 binds to XIAP, an inhibitor of caspases-3, -7, and -9, and triggers its relocation from the cytosol to the nucleus. Overexpression of XAF-1 results in the neutralization of XIAP's ability to inhibit cell death. XAF-1 is normally expressed in all adult and fetal tissues but was found to be present in very low levels in a variety of cancer cell lines. In contrast, XIAP levels have been shown to be high in a majority of cell lines. Low XAF-1 and high basal expression of XIAP may therefore play a critical role in maintaining survival of cancer cell lines. Both IFN-alpha2 and IFN-beta can induce XAF-1 mRNA in all cells examined but induction of XAF-1 protein (as observed by immunoblot analysis) was seen only in cell lines sensitive to the apoptotic effects of IFNs.