Tollip (F4Y5L) Rabbit Monoclonal Antibody#90551,Cell Signaling Technology (CST),90551

Members of the Toll-like receptor (TLR) family, named for the closely related Toll receptor inDrosophila, play a pivotal role in innate immune responses (1-4). TLRs recognize conserved motifs found in various pathogens and mediate defense responses (5-7). Triggering of the TLR pathway leads to the activation of NF-κB and subsequent regulation of immune and inflammatory genes (4). The TLRs and members of the IL-1 receptor family share a conserved stretch of approximately 200 amino acids known as the Toll/Interleukin-1 receptor (TIR) domain (1). Upon activation, TLRs associate with a number of cytoplasmic adapter proteins containing TIR domains, including myeloid differentiation factor 88 (MyD88), MyD88-adapter-like/TIR-associated protein (MAL/TIRAP), TIR domain-containing adapter-inducing IFN-β (TRIF), and Toll-receptor-associated molecule (TRAM) (8-10). This association leads to the recruitment and activation of IRAK1 and IRAK4, which form a complex with TRAF6 to activate TAK1 and IKK (8,11-14). Activation of IKK leads to the degradation of IκB, which normally maintains NF-κB in an inactive state by sequestering it in the cytoplasm.Toll-interacting protein (Tollip) is an adaptor protein discovered to be associated with the IRAK complex and recruited to IL-1R following IL-1 stimulation (4). Overexpression of Tollip results in impaired NF-κB signaling (4). Tollip also directly associates with TLR2 and TLR4, inhibiting TLR-mediated signaling by inhibiting IRAK (5). Studies of Tollip-deficient mice suggest that it plays a role in regulating inflammatory cytokine responses to IL-1 and LPS (6).Akira, S. (2003)J Biol Chem278, 38105-8.Beutler, B. (2004)Nature430, 257-63.Dunne, A. and O'Neill, L.A. (2003)Sci STKE2003, re3.Medzhitov, R. et al. (1997)Nature388, 394-7.Schwandner, R. et al. (1999)J Biol Chem274, 17406-9.Takeuchi, O. et al. (1999)Immunity11, 443-51.Alexopoulou, L. et al. (2001)Nature413, 732-8.Zhang, F.X. et al. (1999)J Biol Chem274, 7611-4.Horng, T. et al. (2001)Nat Immunol2, 835-41.Oshiumi, H. et al. (2003)Nat Immunol4, 161-7.Muzio, M. et al. (1997)Science278, 1612-5.Wesche, H. et al. (1997)Immunity7, 837-47.Suzuki, N. et al. (2002)Nature416, 750-6.Irie, T. et al. (2000)FEBS Lett467, 160-4.Burns, K. et al. (2000)Nat Cell Biol2, 346-51.Zhang, G. and Ghosh, S. (2002)J Biol Chem277, 7059-65.Didierlaurent, A. et al. (2006)Mol Cell Biol26, 735-42.Alternate Namesadapter protein; FLJ33531; IL-1RAcPIP; TOLIP; toll interacting protein; Toll-interacting protein; TOLLIP

adapter protein; FLJ33531; IL-1RAcPIP; TOLIP; toll interacting protein; Toll-interacting protein; TOLLIP