Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations

Srgjan Civciristov; Andrew M. Ellisdon; Ryan Suderman; Cindy K. Pon; Bronwyn A. Evans; Oded Kleifeld; Steven J. Charlton; William S. Hlavacek; Meritxell Canals; Michelle L. Halls

doi:10.1126/scisignal.aan1188

Research ArticleGPCR SIGNALING

Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations

Srgjan Civciristov¹,
Andrew M. Ellisdon²,
Ryan Suderman³,
Cindy K. Pon¹,
Bronwyn A. Evans¹,
Oded Kleifeld²,⁴,
Steven J. Charlton⁵,⁶,
William S. Hlavacek³,
Meritxell Canals¹, and
Michelle L. Halls ¹,*

¹Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
²Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
³Theoretical Biology and Biophysics Group, Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
⁴Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 3200003, Israel.
⁵Cell Signalling Research Group, School of Life Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, UK.
⁶Excellerate Bioscience Ltd, MediCity, Nottingham NG90 6BH, UK.

↵*Corresponding author. Email: michelle.halls{at}monash.edu

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Sci. Signal. 09 Oct 2018:
Vol. 11, Issue 551, eaan1188
DOI: 10.1126/scisignal.aan1188

Srgjan Civciristov

Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.

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Andrew M. Ellisdon

Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.

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Ryan Suderman

Theoretical Biology and Biophysics Group, Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.

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Cindy K. Pon

Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.

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Bronwyn A. Evans

Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.

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Oded Kleifeld

Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 3200003, Israel.

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Steven J. Charlton

Cell Signalling Research Group, School of Life Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham NG7 2UH, UK.Excellerate Bioscience Ltd, MediCity, Nottingham NG90 6BH, UK.

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William S. Hlavacek

Theoretical Biology and Biophysics Group, Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.

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Meritxell Canals

Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.

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Michelle L. Halls

Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.

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For correspondence: michelle.halls@monash.edu

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Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations

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