Multiple phosphorylation sites in RGS16 differentially modulate its GAP activity

FEBS Lett. 2001 Aug 24;504(1-2):16-22. doi: 10.1016/s0014-5793(01)02757-0.


Regulators of G-protein signaling (RGS) are GTPase-activating proteins (GAP) for activated Galpha subunits. We found that mouse RGS16, when expressed in HEK293T cells, is phosphorylated constitutively at serine 194 based on in vivo orthophosphate labeling experiments, while serine 53 is phosphorylated in a ligand-dependent manner upon stimulation by epinephrine in cells expressing the alpha2A adrenergic receptor. Phosphorylation on both sites impairs its GAP activity and subsequent attenuation on heterotrimeric G-protein-stimulated extracellular signal-regulated protein kinase activity. This is the first report of RGS functional downregulation by phosphorylation via a G-protein-coupled receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Enzyme Activation
  • Epinephrine / pharmacology
  • GTPase-Activating Proteins / metabolism*
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Humans
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • Proteins / chemistry
  • Proteins / metabolism*
  • RGS Proteins / chemistry
  • RGS Proteins / metabolism*
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Serine / metabolism


  • ADRA2A protein, human
  • Adra2a protein, mouse
  • GTPase-Activating Proteins
  • Proteins
  • RGS Proteins
  • RGS16 protein
  • Receptors, Adrenergic, alpha-2
  • Serine
  • Mitogen-Activated Protein Kinases
  • Heterotrimeric GTP-Binding Proteins
  • Epinephrine