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J Biomol Screen. 2015 Mar;20(3):341-9. doi: 10.1177/1087057114557233. Epub 2014 Oct 31.

ERK and β-arrestin interaction: a converging point of signaling pathways for multiple types of cell surface receptors.

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BioInvenu Corp., East Hanover, NJ, USA
National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
BioInvenu Corp., East Hanover, NJ, USA.


β-Arrestin, a signal adaptor protein, mediates intracellular signal transductions through protein-protein interactions by bringing two or more proteins in proximity. Extracellular signal-regulated kinase (ERK), a protein kinase in the family of mitogen-activated protein kinases (MAPKs), is involved in various receptor signal pathways. Interaction of ERK with β-arrestin or formation of ERK/β-arrestin signal complex occurs in response to activation of a variety of cell surface receptors. The ERK/β-arrestin signal complex may be a common transducer to converge a variety of extracellular stimuli to similar downstream intracellular signaling pathways. By using a cell-based protein-protein interaction LinkLight assay technology, we demonstrate a direct interaction between ERK and β-arrestin in response to extracellular stimuli, which can be sensitively and quantitatively monitored. Activations of G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), and cytokine receptors promote formation of the ERK/β-arrestin signal complex. Our data indicate that the ERK/β-arrestin signal complex is a common transducer that participates in a variety of receptor signaling pathways. Furthermore, we demonstrate that receptor antagonists or kinase inhibitors can block the agonist-induced ERK and β-arrestin interaction. Thus, the ERK/β-arrestin interaction assay is useful for screening of new receptor modulators.


ERK; extracellular signal-regulated kinases; protein-protein interactions; β-arrestin

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