Phospho-IKKalpha (Ser176)/IKKbeta (Ser177) Rabbit mAb

The NF-κB/Rel transcription factors are present in the cytosol in an inactive state, complexed with the inhibitory IκB proteins (1-3). Most agents that activate NF-κB do so through a common pathway based on phosphorylation-induced, proteasome-mediated degradation of IκB (3-7). The key regulatory step in this pathway involves activation of a high molecular weight IκB kinase (IKK) complex whose catalysis is generally carried out by three tightly associated IKK subunits. IKKα and IKKβ serve as the catalytic subunits of the kinase and IKKγ serves as the regulatory subunit (8,9). Activation of IKK depends upon phosphorylation at Ser177 and Ser181 in the activation loop of IKKβ (Ser176 and Ser180 in IKKα), which causes conformational changes, resulting in kinase activation (10-13). 1.Baeuerle, P.A. and Baltimore, D. (1988) Science 242, 540-6. 2.Beg, A.A. and Baldwin, A.S. (1993) Genes Dev 7, 2064-70. 3.Finco, T.S. et al. (1994) Proc Natl Acad Sci USA 91, 11884-8. 4.Brown, K. et al. (1995) Science 267, 1485-8. 5.Brockman, J.A. et al. (1995) Mol Cell Biol 15, 2809-18. 6.Traenckner, E.B. et al. (1995) EMBO J 14, 2876-83. 7.Chen, Z.J. et al. (1996) Cell 84, 853-62. 8.Zandi, E. et al. (1997) Cell 91, 243-52. 9.Karin, M. (1999) Oncogene 18, 6867-74. 10.DiDonato, J.A. et al. (1997) Nature 388, 548-54. 11.Mercurio, F. et al. (1997) Science 278, 860-6. 12.Johnson, L.N. et al. (1996) Cell 85, 149-58. 13.Delhase, M. et al. (1999) Science 284, 309-13.