Multiple Structural Domains within IκBα Are Required for Its Inducible Degradation by both Cytokines and Phosphatase Inhibitors

摘要: Activation of the transcription factor NF-kappa B by various cellular stimuli involves phosphorylation and subsequent degradation its inhibitor I kappa alpha. Both cytokine tumor necrosis alpha (TNF-alpha) phosphatase calyculin A have been shown to induce rapid In present study, we demonstrate that TNF-alpha stimulate similar although not identical pattern phosphorylation, as demonstrated phosphopeptide mapping. Interestingly, induced both inducers serine-32 serine-36 Furthermore, TNF-alpha- A-induced appears require same structural domains within addition N-terminal sites C-terminal sequences, each five ankyrin-like repeats is critically required for inducible this inhibitor. Together, these studies suggest cytokines inhibitors regulated site-specific requires multiple domains.