Formation of a ternary complex among NHERF1, beta-arrestin, and parathyroid hormone receptor.

The Journal of Biological Chemistry
Christoph KlenkM J Lohse

Abstract

β-Arrestins are crucial regulators of G-protein coupled receptor (GPCR) signaling, desensitization, and internalization. Despite the long-standing paradigm that agonist-promoted receptor phosphorylation is required for β-arrestin2 recruitment, emerging evidence suggests that phosphorylation-independent mechanisms play a role in β-arrestin2 recruitment by GPCRs. Several PDZ proteins are known to interact with GPCRs and serve as cytosolic adaptors to modulate receptor signaling and trafficking. Na(+)/H(+) exchange regulatory factors (NHERFs) exert a major role in GPCR signaling. By combining imaging and biochemical and biophysical methods we investigated the interplay among NHERF1, β-arrestin2, and the parathyroid hormone receptor type 1 (PTHR). We show that NHERF1 and β-arrestin2 can independently bind to the PTHR and form a ternary complex in cultured human embryonic kidney cells and Chinese hamster ovary cells. Although NHERF1 interacts constitutively with the PTHR, β-arrestin2 binding is promoted by receptor activation. NHERF1 interacts directly with β-arrestin2 without using the PTHR as an interface. Fluorescence resonance energy transfer studies revealed that the kinetics of PTHR and β-arrestin2 interactions were modulated ...Continue Reading

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Citations

Feb 9, 2011·Nature Reviews. Endocrinology·Gilbert Vassart, Sabine Costagliola
May 23, 2012·The Journal of Biological Chemistry·Shaista P NisarStuart J Mundell
Aug 30, 2011·Pharmacological Reviews·Juan A Ardura, Peter A Friedman
Jun 21, 2015·Pharmacological Reviews·Dustin R WalshPeter A Friedman
Oct 27, 2011·European Journal of Immunology·Yi-Qun KuangDenis J Dupré
Jan 11, 2013·Physiological Reviews·Sascha Kopic, John P Geibel
Mar 7, 2014·The Journal of Biological Chemistry·Wei KanAlan V Smrcka
May 23, 2015·American Journal of Physiology. Renal Physiology·Corey J KetchemEleanor D Lederer
Mar 21, 2012·Biochemistry·Tatyana MamonovaPeter A Friedman

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