Product Pathways - NF-kappaB Signaling

Phospho-NF-κB p105 (Ser933) (178F3) Rabbit mAb (IHC Specific) #4808

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Applications	Reactivity	MW (kDa)	Source	Isotype
IHC-P	H	105	Rabbit	IgG

Applications Key:  IHC-P=Immunohistochemistry (Paraffin)
Reactivity Key:  H=Human
Species enclosed in parentheses are predicted to react based on 100% sequence homology. Species cross-reactivity is determined by Western blot.

Specificity / Sensitivity

Phospho-NF-kappaB p105 (Ser933) (178F3) Rabbit mAb detects endogenous levels of p105NF-kappaB only when phosphorylated at serine 933.

Source / Purification

Monoclonal antibodies are produced by immunizing rabbits with a synthetic phospho-peptide (KLH-coupled) corresponding to amino acids around Ser933 of NF-kappaB p105.

Background

Transcription factors of the nuclear factor kappaB (NF-κB)/Rel family play a pivotal role in inflammatory and immune responses (1,2). There are five family members in mammals: RelA, c-Rel, RelB, NF-κB1 (p105/p50) and NF-κB2 (p100/p52). Both p105 and p100 are proteolytically processed by the proteasome to produce p50 and p52, respectively. Rel proteins bind p50 and p52 to form dimeric complexes that bind DNA and regulate transcription. In unstimulated cells, NF-κB is sequestered in the cytoplasm by IκB inhibitory proteins (3-5). NF-κB-activating agents can induce the phosphorylation of IκB proteins, targeting them for rapid degradation through an ubiquitin-proteasome pathway and releasing NF-κB to enter the nucleus where it regulates gene expression (6-8). NIK and IKK-α (IKK1) regulate the phosphorylation and processing of NF-κB2 (p100) to produce p52, which is then translocated to the nucleus (9-11).

Following IKK-mediated phosphorylation of p105 NF-kappaB at multiple sites (Ser921, 923, 927 and 933) on its carboxy-terminus, SCFbeta-TrCP mediated processing produces the 50 kDa active form p50 (12,13).

1. Baeuerle, P.A. and Henkel, T. (1994) Annu Rev Immunol 12, 141-79.
2. Baeuerle, P.A. and Baltimore, D. (1996) Cell 87, 13-20.
3. Haskill, S. et al. (1991) Cell 65, 1281-9.
4. Thompson, J.E. et al. (1995) Cell 80, 573-82.
5. Whiteside, S.T. et al. (1997) EMBO J 16, 1413-26.
6. Traenckner, E.B. et al. (1995) EMBO J 14, 2876-83.
7. Scherer, D.C. et al. (1995) Proc Natl Acad Sci USA 92, 11259-63.
8. Chen, Z.J. et al. (1996) Cell 84, 853-62.
9. Senftleben, U. et al. (2001) Science 293, 1495-9.
10. Coope, H.J. et al. (2002) EMBO J 21, 5375-85.
11. Xiao, G. et al. (2001) Mol Cell 7, 401-9.
12. Heissmeyer, V. et al. (2001) Mol. Cell. Biol. 21, 1024-1035.
13. Orian, A. et al. (2000) EMBO J. 19, 2580-2591.

Application References

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Companion Products

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Rabbit Monoclonals Produced Using Epitomics® Technology, U.S. Patent No. 5,675,063.