Phospho-IKKγ (Ser376) Antibody #2689

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).
Activation of the NF-κB pathway by the T-cell lymphotrophic virus Tax protein or by TNF-α treatment leads to IKKβ-dependent phosphorylation of human IKKγ primarily at Ser376 (14). In mouse, mutation of the orthologous residue (Ser369) to alanine leads to enhanced IKKγ-mediated stimulation of IKKβ kinase activity (15).