title: ERK and β-arrestin interaction: a converging point of signaling pathways for multiple types of cell surface receptors.
abstract: 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.
authors.affiliation: BioInvenu Corp., East Hanover, NJ, USA haifeng.eishingdrelo@bioinvenu.com wzheng@mail.nih.gov.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Eishingdrelo
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: BioInvenu Corp., East Hanover, NJ, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: BioInvenu Corp., East Hanover, NJ, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: BioInvenu Corp., East Hanover, NJ, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Eishingdrelo
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Dai
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: McKew
authors.affiliation: National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
mesh_terms: D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D017930:Genes, Reporter; D057166:High-Throughput Screening Assays; D006801:Humans; D011485:Protein Binding; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D018121:Receptors, Cytokine / Q000819:agonists / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins; D020794:Receptor Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: ERK; extracellular signal-regulated kinases; protein-protein interactions; β-arrestin