Formation of a ternary complex among NHERF1, beta-arrestin, and parathyroid
hormone receptor
C. Klenk, T. Vetter, A. Zurn, J. Vilardaga, P. Friedman, B. Wang, and M. Lohse. J Biol Chem, 285 (39):
30355-62(September 2010)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..
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.
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.
%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
}