G protein-coupled receptor cross-talk: pivotal roles of protein phosphorylation and protein-protein interactions

Cell Signal. 2003 Jun;15(6):549-57. doi: 10.1016/s0898-6568(02)00151-1.


G protein-coupled receptors are dynamically regulated. Such regulation is frequently associated with covalent posttranslational modifications, such as phosphorylation, and with regulatory elements. G protein-coupled receptor kinases and casein kinase 1alpha play key roles in agonist-dependent receptor phosphorylations. Cross-talk between different receptors frequently involves second messenger-activated proteins, such as protein kinase C and protein kinase A. There is some evidence indicating that such kinases may not only turn off receptors but also switch their coupling to different G proteins. Receptor tyrosine kinases may phosphorylate and regulate G protein-coupled receptors and recent evidence indicates that other kinases, such as Akt/protein kinase B and phosphoinositide 3-kinase, may participate in such regulations as integrators of signalling. Recent approaches have shed new light on G protein-coupled receptor interactions that provide novel mechanisms of action and regulation. G protein-coupled receptor activities go beyond G proteins and receptors can be partners of exquisitely assembled signalling complexes through molecular bridges composed of multidomain proteins. The possibilities of interaction increase enormously through the diversity of structural and functional domains present in complex proteins, many of them just known as predicted sequences.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Macromolecular Substances
  • Phosphoprotein Phosphatases / metabolism
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Kinases / metabolism
  • Proteomics
  • RGS Proteins / metabolism
  • Receptor Cross-Talk*
  • Receptors, Cell Surface / metabolism*


  • Macromolecular Substances
  • Phosphoproteins
  • RGS Proteins
  • Receptors, Cell Surface
  • Protein Kinases
  • Phosphoprotein Phosphatases
  • Heterotrimeric GTP-Binding Proteins