%0 Journal Article %1 Klenk2010a %A Klenk, C. %A Vetter, T. %A Zurn, A. %A Vilardaga, J. P. %A Friedman, P. A. %A Wang, B. %A Lohse, M. J. %D 2010 %J J Biol Chem %K 1/genetics/*metabolism Animals Antiporter/genetics/*metabolism Arrestins/genetics/*metabolism CHO Complexes/genetics/*metabolism Cricetinae Cricetulus Hormone, Humans Multiprotein Parathyroid Phosphoproteins/genetics/*metabolism Protein Quaternary Signal Sodium-Hydrogen Structure, Transduction/physiology Type Receptor Cell %N 39 %P 30355-62 %T Formation of a ternary complex among NHERF1, beta-arrestin, and parathyroid hormone receptor %U http://www.ncbi.nlm.nih.gov/pubmed/20656684 %V 285 %X beta-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 beta-arrestin2 recruitment, emerging evidence suggests that phosphorylation-independent mechanisms play a role in beta-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, beta-arrestin2, and the parathyroid hormone receptor type 1 (PTHR). We show that NHERF1 and beta-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, beta-arrestin2 binding is promoted by receptor activation. NHERF1 interacts directly with beta-arrestin2 without using the PTHR as an interface. Fluorescence resonance energy transfer studies revealed that the kinetics of PTHR and beta-arrestin2 interactions were modulated by NHERF1. These findings suggest a model in which NHERF1 may serve as an adaptor, bringing beta-arrestin2 into close proximity to the PTHR, thereby facilitating beta-arrestin2 recruitment after receptor activation.

@article{Klenk2010a, abstract = {beta-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 beta-arrestin2 recruitment, emerging evidence suggests that phosphorylation-independent mechanisms play a role in beta-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, beta-arrestin2, and the parathyroid hormone receptor type 1 (PTHR). We show that NHERF1 and beta-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, beta-arrestin2 binding is promoted by receptor activation. NHERF1 interacts directly with beta-arrestin2 without using the PTHR as an interface. Fluorescence resonance energy transfer studies revealed that the kinetics of PTHR and beta-arrestin2 interactions were modulated by NHERF1. These findings suggest a model in which NHERF1 may serve as an adaptor, bringing beta-arrestin2 into close proximity to the PTHR, thereby facilitating beta-arrestin2 recruitment after receptor activation.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Klenk, C. and Vetter, T. and Zurn, A. and Vilardaga, J. P. and Friedman, P. A. and Wang, B. and Lohse, M. J.}, biburl = {https://www.bibsonomy.org/bibtex/22b74a1ba2853d3b8ca40ea18c72d6ac9/pharmawuerz}, comment = {2943313}, endnotereftype = {Journal Article}, groups = {private}, interhash = {bb5cd0cc62d600ad5bdfa52f9d5f0f96}, intrahash = {2b74a1ba2853d3b8ca40ea18c72d6ac9}, issn = {1083-351X (Electronic) 0021-9258 (Linking)}, journal = {J Biol Chem}, keywords = {1/genetics/*metabolism Animals Antiporter/genetics/*metabolism Arrestins/genetics/*metabolism CHO Complexes/genetics/*metabolism Cricetinae Cricetulus Hormone, Humans Multiprotein Parathyroid Phosphoproteins/genetics/*metabolism Protein Quaternary Signal Sodium-Hydrogen Structure, Transduction/physiology Type Receptor Cell}, month = {Sep 24}, note = {Klenk, Christoph Vetter, Thorsten Zurn, Alexander Vilardaga, Jean-Pierre Friedman, Peter A Wang, Bin Lohse, Martin J DK069998/DK/NIDDK NIH HHS/United States DK087688/DK/NIDDK NIH HHS/United States DK54171/DK/NIDDK NIH HHS/United States Research Support, N.I.H., Extramural United States The Journal of biological chemistry J Biol Chem. 2010 Sep 24;285(39):30355-62. Epub 2010 Jul 23.}, number = 39, pages = {30355-62}, shorttitle = {Formation of a ternary complex among NHERF1, beta-arrestin, and parathyroid hormone receptor}, timestamp = {2010-12-14T18:20:39.000+0100}, title = {Formation of a ternary complex among NHERF1, beta-arrestin, and parathyroid hormone receptor}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20656684}, volume = 285, year = 2010 }