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Please use this identifier to cite or link to this item: http://hdl.handle.net/1783.1/2457
Title: G16-mediated activation of nuclear factor κB by the adenosine A1 receptor involves c-Src, protein kinase C, and ERK signaling
Authors: Liu, Andrew M. F.
Wong, Yung-Hou
Keywords: Adenosine A
Cyclohexyladenosine
Phospholipase C
Anti-inflammatory actions
Issue Date: Dec-2004
Citation: Journal of biological chemistry, v. 279, no. 51, Dec. 2004, p. 53196-53204
Abstract: The Gi-linked adenosine A1 receptor has been shown to mediate anti-inflammatory actions, possibly via modulation of the transcription factor nuclear factor-κB (NFκB). Here we demonstrate that an adenosine A1 agonist, N6-cyclohexyladenosine (CHA), activated IKKα/β phosphorylation through PTX-insensitive G proteins in human lymphoblastoma Reh cells. To delineate the mechanism of action, different PTX-insensitive G proteins were expressed in human embryonic kidney 293 cells. Only Gα16 supported the CHA-induced IKK phosphorylation and NFκB-driven luciferase activity in time-dependent, dose-dependent, and PTX-insensitive manners. Gβγ subunits also modulated IKK/NFκB, as indicated by the stimulatory actions of Gβ1γ2 and the abrogation of CHA-induced response by transducin. The participation of phospholipase Cβ, protein kinase C, and calmodulin-dependent kinase II in CHA-induced IKK/NFκB activation were demonstrated by employing specific inhibitors and dominant-negative mutants. Inhibition of c-Src and numerous intermediates along the extracellular signal-regulated (ERK) kinase cascade including Ras, Raf-1 kinase, and MEK1/2 abolished the CHA-induced IKK/NFκB activation. Although c-Jun N-terminal kinase and p38 MAPK were also activated by CHA, they were not required for the IKK/NFκB regulation. Similar results were obtained using Reh cells. These data suggest that the G16-mediated activation of IKK/NFκB by CHA required a complex signaling network composed of multiple intermediates.
Rights: We would like to give credit to American Society for Biochemistry and Molecular Biology for granting us permission to repost this article
URI: http://hdl.handle.net/1783.1/2457
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