Cell Signaling Technology

Product Pathways - NF-kB Signaling

Tollip Antibody #4748

Applications Reactivity Sensitivity MW (kDa) Source
W H Mk Endogenous 33 Rabbit

Applications Key:  W=Western Blotting
Reactivity Key:  H=Human  Mk=Monkey
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.

Protocols

Specificity / Sensitivity

Tollip Antibody detects endogenous levels of total Tollip protein.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding cysteine 229 of human Tollip. Antibodies are purified by protein A and peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of extracts from SW620, HeLa and COS cells, using Tollip Antibody.

Background

Members of the Toll-like receptor (TLR) family, named for the closely related Toll receptor in Drosophila, play a pivotal role in innate immune responses (1-3). TLRs recognize conserved motifs found in various pathogens and mediate defense responses. Triggering of the TLR pathway leads to the activation of NF-κB and subsequent regulation of immune and inflammatory genes. The TLRs and members of the IL-1 receptor family share a conserved stretch of approximately 200 amino acids known as the TIR domain. Upon activation, TLRs associate with a number of cytoplasmic adaptor proteins containing TIR domains including MyD88 (myeloid differentiation factor), MAL/TIRAP (MyD88-adaptor-like/TIR-associated protein), TRIF (Toll-receptor-associated activator of interferon), and TRAM (Toll-receptor-associated molecule). This association leads to the recruitment and activation of IRAK1 and IRAK4, which form a complex with TRAF6 to activate TAK1 and IKK. Activation of IKK leads to the degradation of IκB that normally maintains NF-κB inactivity by sequestering it in the cytoplasm.

Tollip (Toll interacting protein) is an adaptor protein discovered to be associated with the IRAK complex and recruited to IL1-R following IL-1 stimulation (4). Overexpression of Tollip results in impaired NF-κB signaling (4). Tollip also associates directly with TLR2 and TLR4 and inhibits TLR-mediated signaling through inhibition of IRAK (5). Studies of Tollip deficient mice suggest that it plays a role in the regulation of inflammatory cytokines in response to IL-1 and LPS (6).

  1. Akira, S. (2003) J Biol Chem 278, 38105-8.
  2. Beutler, B. (2004) Nature 430, 257-63.
  3. Dunne, A. and O'Neill, L.A. (2003) Sci STKE 2003, re3.
  4. Burns, K. et al. (2000) Nat. Cell Biol. 2, 346-351.
  5. Zhang, G. and Ghosh, S. (2002) J. Biol. Chem. 277, 7059-7065.
  6. Didierlaurent, A. et al. (2006) Mol. Cell Biol. 26, 735-742.

Application References

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Companion Products

This product is intended for research purposes only. The product is not intended to be used for therapeutic or diagnostic purposes in humans or animals.

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