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Arrestin-dependent activation of ERK and Src family kinases

Erik G Strungs1, Louis M Luttrell

  • 1Department of Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA.

Handbook of Experimental Pharmacology
|December 3, 2013
PubMed

Insights

Mammalian arrestins bind G protein-coupled receptors, regulating desensitization and signaling. Nonvisual arrestins also mediate receptor trafficking and form signaling complexes, impacting cell growth and survival.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Mammalian arrestins (visual and nonvisual) bind G protein-coupled receptors (GPCRs) upon stimulation.
  • Arrestin binding desensitizes receptors by blocking G protein coupling.
  • Nonvisual arrestins act as adaptors for receptor endocytosis and trafficking.

Purpose of the Study:

  • To elucidate the multifaceted roles of arrestins in GPCR regulation and signaling.
  • To explore arrestin's function as scaffolds for signaling complexes.
  • To investigate arrestin-mediated regulation of kinase pathways.

Main Methods:

  • The study is primarily a review and synthesis of existing literature on arrestin function.
  • Focuses on molecular mechanisms of arrestin-GPCR interaction.
  • Examines arrestin's role in clathrin-mediated endocytosis and signaling complex formation.

Main Results:

  • Arrestins mediate GPCR desensitization and internalization.
  • Nonvisual arrestins regulate receptor sequestration, trafficking, recycling, and degradation.
  • Arrestins form signaling "signalsome" complexes, recruiting kinases like Src and ERK1/2.
  • Arrestin scaffolding influences kinase activity, duration, and substrate specificity.

Conclusions:

  • Arrestin binding transitions receptors from a transient G protein-coupled state to a persistent, internalized arrestin-coupled state.
  • Arrestin-mediated signaling pathways involving Src and ERK1/2 impact cellular processes like growth, migration, and survival.
  • Arrestins are critical regulators of GPCR signaling, desensitization, trafficking, and downstream cellular responses.

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