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

Methods Development

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

Eishingdrelo, Haifeng; Sun, Wei; Li, Hua; Wang, Li; Eishingdrelo, Alex; Dai, Sheng; McKew, John C; Zheng, Wei;

Keywords

  • Arrestins/ genetics
  • Arrestins/ metabolism
  • Cell Line
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases/ genetics
  • Extracellular Signal-Regulated MAP Kinases/ metabolism
  • Gene Expression
  • Genes, Reporter
  • High-Throughput Screening Assays
  • Humans
  • Protein Binding
  • Receptor Protein-Tyrosine Kinases/ metabolism
  • Receptors, Cell Surface/ agonists
  • Receptors, Cell Surface/ antagonists & inhibitors
  • Receptors, Cell Surface/ metabolism
  • Receptors, Cytokine/ agonists
  • Receptors, Cytokine/ metabolism
  • Receptors, G-Protein-Coupled/ agonists
  • Receptors, G-Protein-Coupled/ antagonists & inhibitors
  • Receptors, G-Protein-Coupled/ metabolism
  • Signal Transduction/ drug effects

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