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RGS-Insensitive Gα Subunits: Probes of Gα Subtype-Selective Signaling and Physiological Functions of RGS Proteins

  • Kuljeet Kaur
  • Jason M. Kehrl
  • Raelene A. Charbeneau
  • Richard R. NeubigEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 756)

Abstract

The Regulator of G protein Signaling (RGS) proteins were identified as a family in 1996 and humans have more than 30 such proteins. Their best known function is to suppress G Protein-Coupled Receptors (GPCR) signaling by increasing the rate of Gα turnoff through stimulation of GTPase activity (i.e., GTPase acceleration protein or GAP activity). The GAP activity of RGS proteins on the Gαi and Gαq family of G proteins can terminate signals initiated by both α and βγ subunits. RGS proteins also serve as scaffolds, assembling signal-regulating modules. Understanding the physiological roles of RGS proteins is of great importance, as GPCRs are major targets for drug development. The traditional method of using RGS knockout mice has provided some information about the role of RGS proteins but in many cases effects are modest, perhaps because of redundancy in RGS protein function. As an alternative approach, we have utilized a glycine-to-serine mutation in the switch 1 region of Gα subunits that prevents RGS binding. The mutation has no known effects on Gα binding to receptor, Gβγ, or effectors. Alterations in function resulting from the G  >  S mutation imply a role for both the specific mutated Gα subunit and its regulation by RGS protein activity. Mutant rodents expressing these G  >  S mutant Gα subunits have strong phenotypes and provide important information about specific physiological functions of Gαi2 and Gαo and their control by RGS. The conceptual framework behind this approach and a summary of recent results is presented in this chapter.

Key words

G protein-coupled receptor Heterotrimeric G protein Regulator of G protein signaling protein GTPase-activating protein Signal transduction 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Kuljeet Kaur
    • 1
  • Jason M. Kehrl
    • 1
  • Raelene A. Charbeneau
    • 1
  • Richard R. Neubig
    • 2
    Email author
  1. 1.Department of PharmacologyThe University of Michigan Medical SchoolAnn ArborUSA
  2. 2.Departments of Pharmacology and Internal MedicineThe University of Michigan Medical SchoolAnn ArborUSA

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