The NF-kappaB/Rel transcription factors are present in the cytosol in an inactive state, complexed with the inhibitory IkappaB-alpha protein (1-5). In response to many different NF-kappaB-inducing agents including T-cell mitogens, proinflammatory cytokines, and viral transactivators the inhibitory IkappaB-alpha is rapidly phosphorylated and degraded (2). Phosphorylation of IkappaB-alpha at Ser32 and Ser36 has been shown to stimulate conjugation with ubiquitin and subsequent degradation of IkappaB-alpha (3). Activation of NF-kappaB can also be achieved after tyrosine phosphorylation of IkappaBalpha at tyrosine 42, an event that also ultimately leads to the dissociation of NF-kappaB and IkappaBalpha (4). Phosphorylation of IkappaB-alpha at Ser32 and Tyr42 is critical for activation of NF-kappaB, which then translocates to the nucleus and induces transcription of genes that protect organism (1-5).
Delta-Notch Signaling Pathway
Toll-like receptor signaling pathway
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