beta-Arrestin1 interacts with the G-protein subunits beta1gamma2 and promotes beta1gamma2-dependent Akt signalling for NF-kappaB activation.

beta-Arrestins are known to regulate G-protein signalling through interactions with their downstream effectors. In the present study, we report that beta-arrestin1 associates with the G-protein beta1gamma2 subunits in transfected cells, and purified beta-arrestin1 interacts with G(beta1gamma2) derived from in vitro translation. Deletion mutagenesis of beta-arrestin1 led to the identification of ...
a region, comprising amino acids 181-280, as being responsible for its interaction with G(beta1gamma2). Overexpression of beta-arrestin1 facilitates G(beta1gamma2)-mediated Akt phosphorylation, and inhibition of endogenous beta-arrestin1 expression by siRNA (small interfering RNA) diminishes this effect. Through investigation of NF-kappaB (nuclear factor kappaB), a transcription factor regulated by Akt signalling, we have found that overexpression of beta-arrestin1 significantly enhances G(beta1gamma2)-mediated nuclear translocation of NF-kappaB proteins and expression of a NF-kappaB-directed luciferase reporter. Overexpression of beta-arrestin1 also promotes bradykinin-induced, G(betagamma)-mediated NF-kappaB luciferase-reporter expression, which is reverted by silencing the endogenous beta-arrestin1 with a specific siRNA. These results identify novel functions of beta-arrestin1 in binding to the beta1gamma2 subunits of heterotrimeric G-proteins and promoting G(betagamma)-mediated Akt signalling for NF-kappaB activation.
Mesh Terms:
Arrestins, Blotting, Western, Cell Line, Electrophoretic Mobility Shift Assay, GTP-Binding Protein beta Subunits, GTP-Binding Proteins, HeLa Cells, Humans, Immunoprecipitation, NF-kappa B, Phosphorylation, Protein Binding, Proto-Oncogene Proteins c-akt, RNA, Small Interfering, Sequence Deletion, Signal Transduction
Biochem. J.
Date: Jan. 01, 2009
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