Cell Signaling Technology

Product Pathways - NF-kappaB 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.

Specificity / Sensitivity

Tollip Antibody detects endogenous levels of total Tollip protein.

Source / Purification

Polyclonal antibodies are prepared by immunizing rabbits with a synthetic peptide (KLH-coupled) 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 for in vitro research use only and is not intended for use in humans or animals. This product is not intended for use as therapeutic or in diagnostic procedures.

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