Β-Arrestin 2 Regulates Toll-Like Receptor 4-Mediated Apoptotic Signalling Through Glycogen Synthase Kinase-3β
Document Type
Article
Publication Date
8-1-2010
Description
Toll-like receptor 4 (TLR4), a key member of the TLR family, has been well characterized by its function in the induction of inflammatory products of innate immunity. However, the involvement of TLR4 in a variety of apoptotic events by an unknown mechanism has been the focus of great interest. Our investigation found that TLR4 promoted apoptotic signalling by affecting the glycogen synthase kinase-3β (GSK-3β) pathway in a serum-deprivation- induced apoptotic paradigm. Serum deprivation induces GSK-3β activation in a pathway that leads to subsequent cell apoptosis. Intriguingly, this apoptotic cascade is amplified in presence of TLR4 but greatly attenuated by β-arrestin 2, another critical molecule implicated in TLR4-mediated immune responses. Our data suggest that the association of β-arrestin 2 with GSK-3β contributes to the stabilization of phospho-GSK-3β, an inactive form of GSK-3β. It becomes a critical determinant for the attenuation of TLR4-initiated apoptosis by β-arrestin 2. Taken together, we demonstrate that the TLR4 possesses the capability of accelerating GSK-3β activation thereby deteriorating serum-deprivation-induced apoptosis; β-arrestin 2 represents an inhibitory effect on the TLR4-mediated apoptotic cascade, through controlling the homeostasis of activation and inactivation of GSK-3β.
Citation Information
Li, Hui; Sun, Xiuli; Lesage, Gene; Zhang, Yi; Liang, Zhihou; Chen, Jixiang; Hanley, Gregory; He, Lei; Sun, Shenggang; and Yin, Deling. 2010. Β-Arrestin 2 Regulates Toll-Like Receptor 4-Mediated Apoptotic Signalling Through Glycogen Synthase Kinase-3β. Immunology. Vol.130(4). 556-563. https://doi.org/10.1111/j.1365-2567.2010.03256.x PMID: 20497256 ISSN: 0019-2805