Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues.

摘要: The response of mammalian cells to stress is controlled by transcriptional regulatory proteins such as nuclear factor kappa B (NF-kappa B) induce a wide variety early genes. In this report, we show that exposure hypoxia (0.02% O2) results in I alpha degradation, increased NF-kappa DNA binding activity, and transactivation reporter gene construct containing two sites. Pretreatment with protein tyrosine kinase inhibitors the dominant negative allele c-Raf-1 (Raf 301) inhibited binding, constructs hypoxia. To demonstrate direct link between changes phosphorylation pattern activation, immunoprecipitated after varying times hypoxic found its status during exposure. Inhibition transfer phosphoryl groups onto prevented degradation binding. comparison other activators phorbol myristate acetate or tumor necrosis factor, did not detect following treatment either these agents. These suggest an important proximal step which precedes dissociation from B.