casein-kinase-ii and thiazolyl-blue

NF-kappaB activation is an important mechanism of mammalian UV response to protect cells. UV-induced NF-kappaB activation depends on the casein kinase II (CK2) phosphorylation of IkappaBalpha at a cluster of C-terminal sites, but how it is regulated remains unclear. Here we demonstrate that beta-arrestin2 can function as an effective suppressor of UV-induced NF-kappaB activation through its direct interaction with IkappaBalpha. CK2 phosphorylation of beta-arrestin2 blocks its interaction with IkappaBalpha and abolishes its suppression of NF-kappaB activation, indicating that the beta-arrestin2 phosphorylation is critical. Moreover, stimulation of beta2-adrenergic receptors, a representative of G-protein-coupled receptors in epidermal cells, promotes dephosphorylation of beta-arrestin2 and its suppression of NF-kappaB activation. Consequently, the beta-arrestin2 suppression leads to promotion of UV-induced cell death, which is also under regulation of beta-arrestin2 phosphorylation. Thus, beta-arrestin2 is identified as a phosphorylation-regulated suppressor of UV response and this may play a functional role in the response of epidermal cells to UV.

Topics: Apoptosis; Arrestins; beta-Arrestins; Binding Sites; Casein Kinase II; Cell Death; Cell Line, Tumor; Cell Nucleus; Cell Separation; DNA Fragmentation; Dose-Response Relationship, Radiation; Epidermis; Flow Cytometry; Humans; Immunoblotting; Immunoprecipitation; In Situ Nick-End Labeling; Models, Biological; Models, Statistical; NF-kappa B; Phosphorylation; Plasmids; Protein Structure, Tertiary; Receptors, G-Protein-Coupled; Reverse Transcriptase Polymerase Chain Reaction; Tetrazolium Salts; Thiazoles; Time Factors; Transfection; Ultraviolet Rays