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The origin and evolution of G protein-coupled receptor kinases

Arcady Mushegian1, Vsevolod V Gurevich, Eugenia V Gurevich

  • 1Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.

Plos One
|March 24, 2012
PubMed

Insights

G protein-coupled receptor (GPCR) kinases (GRKs) evolved early in eukaryotes before animals. These crucial signaling enzymes rapidly diversified in Metazoa to enable swift cellular communication.

Area of Science:

  • Molecular Biology
  • Evolutionary Biology
  • Biochemistry

Background:

  • G protein-coupled receptor (GPCR) kinases (GRKs) are essential for desensitizing GPCRs by phosphorylating activated receptors.
  • This phosphorylation promotes arrestin binding, uncoupling receptors from G proteins and regulating cellular signaling.
  • The early evolutionary history and origin of GRKs across eukaryotic lineages remain largely unexplored.

Purpose of the Study:

  • To investigate the ancient origins and evolutionary trajectory of G protein-coupled receptor kinases (GRKs).
  • To understand the molecular mechanisms underlying GRK emergence and diversification.
  • To identify the earliest appearance of GRK lineages in eukaryotic evolution.

Main Methods:

  • Phylogenetic analysis of GRK protein sequences across diverse eukaryotic taxa.
  • Comparative genomics to trace the insertion of kinase domains into RGS domains.
  • Bioinformatic analysis of GRK structural components and conserved domains.

Main Results:

  • GRKs originated early in eukaryotic evolution through the insertion of a kinase domain into an RGS domain.
  • Two ancient GRK clades are present in early metazoans like Trichoplax adhaerens.
  • GRK-like proteins are found in protists, oomycetes, and brown algae, predating the origin of Metazoa.
  • Distinct N- and C-terminal domains evolved for membrane recruitment and receptor interaction in GRK families.
  • GRK expansion in Metazoa likely supported rapid signaling adjustments in motile animals.

Conclusions:

  • GRKs emerged prior to the animal kingdom, with significant diversification occurring within Metazoa.
  • The evolution of GRKs provided essential mechanisms for rapid and adaptable cellular signaling in early animals.
  • Understanding GRK evolution offers insights into the fundamental processes of signal transduction regulation.

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