Antigen:
peptide corresponding to amino acids 436-449 of human TRAF6
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Host:
rabbit
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Application(s):
WB
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Tumor necrosis factor (TNF)-induced signaling is mediated through association of TNF receptor (TNFR) with adaptor proteins, such as TNF receptor-associated factors (TRAFs). TRAFs form a family of cytoplasmic adapter proteins that mediate signal transduction from many members of the TNF-receptor superfamily (e.g., RANK, CD30, CD40, etc.) and the interleukin-1 receptor. The carboxy-terminal region of TRAFs is required for self-association and interaction with receptor cytoplasmic domains following ligand-induced oligomerization. Recent molecular cloning studies have led to identification of seven TRAFs (TRAF1-TRAF7).1,2,3,4 TRANCE/OPGL activates the antiapoptotic serine/threonine kinase Akt/PKB through a signaling complex involving c-Src and TRAF6.5 Mice deficient in TNF receptor-associated factor 6 (TRAF6) are osteopetrotic with defects in bone remodeling and tooth eruption due to impaired osteoclast function.6 Like TRAF2 and TRAF3, TRAF6 is also essential for perinatal and postnatal survival. These findings establish unexpectedly diverse and critical roles for TRAF6 in perinatal and postnatal survival, bone metabolism, LPS, and cytokine signaling. RANK (TRANCE receptor) interacts with various TRAFs through distinct motifs and activates NF-κB via a novel TRAF6 interaction motif, which then activates NIK, thus leading to NF-κB activation.7 Over-expression of TRAF6 activates JNK, p38, or IKK in the absence of extracellular stimulation.
1
Cheng, G., Cleary, A.M., Ye, Z.S., et al. Involvement of CRAF1, a relative of TRAF, in CD40 signaling. Science 267(5203) 1494-8 (1995).
2
Nakano, H., Oshima, H., Chung, W., et al. TRAF5, an activator of NF-κB and putative signal transducer for the lymphotoxin-β receptor. J Biol Chem 271(25) 14661-4 (2011).
3
Rothe, M., Wong, S.C., Henzel, W.J., et al. A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor. Cell 78(4) 681-92 (1994).
4
Cao, Z., Xiong, J., Takeuchi, M., et al. TRAF6 is a signal transducer for interleukin-1. Nature 383 443-446 (1996).
5
Wong, B.R., Besser, D., Kim, N., et al. TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol Cell 4(6) 1041-9 (1999).
6
Lomaga, M.A., Yeh, W.C., Sarosi, I., et al. TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev 13(8) 1015-24 (1999).
7
Darnay, B.G., Ni, J., Moore, P.A., et al. Activation of NF-kappa.B by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-κB-inducing kinase: Identification of a novel TRAF6 interaction motif. J Biol Chem 274(12) 7724-31 (1999).
