Differential regulation of G-protein-mediated signaling by chemokine receptors

J Biol Chem. 1996 Sep 6;271(36):21814-9. doi: 10.1074/jbc.271.36.21814.


Monocyte chemoattractant protein-1 (MCP-1) is a member of a family of chemotactic cytokines that induce directed migration of leukocytes via activation of seven-transmembrane domain receptors. To identify G-proteins that couple to the two forms of the MCP-1 receptor, as well as to related chemokine receptors, we have performed cotransfection experiments in mammalian cells. In COS-7 cells, the type A and type B MCP-1 receptors coupled to Galphai, Galphaq, and Galpha16, whereas the macrophage inflammatory protein-1alpha/RANTES (regulated on activation, normal T cell-expressed and secreted) receptor (C-CR1) coupled to Galphai and Galphaq but failed to couple to Galpha16. In HEK-293 cells, however, the MCP-1 receptors and C-CR1 coupled to Galphaq but failed to couple to Galpha16. In contrast, the interleukin-8 and C5a receptors did not couple to Galphaq in either COS-7 or HEK-293 cells but did couple to Galpha16. Exchange of intracellular loops between the MCP-1 and interleukin-8 receptors to create chimeric receptors revealed that the third loop of the MCP-1 receptor accounted for virtually all of the coupling to Galphaq. We conclude that the MCP-1 and related chemokine receptors couple to multiple G-proteins, that coupling is cell type-specific, and that the third intracellular loop of the C-C type receptors mediates Galphaq coupling.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / metabolism
  • Cell Line
  • Chemokine CCL2 / metabolism*
  • Chemokine CCL5 / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Hydrolysis
  • Inositol Phosphates / metabolism
  • Molecular Sequence Data
  • Phosphatidylinositols / metabolism
  • Protein Structure, Secondary
  • Receptor, Anaphylatoxin C5a
  • Receptors, CCR2
  • Receptors, Chemokine*
  • Receptors, Complement / metabolism
  • Receptors, Cytokine / metabolism*
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-8A
  • Signal Transduction*
  • Structure-Activity Relationship
  • Substrate Specificity
  • Virulence Factors, Bordetella / pharmacology
  • beta-Adrenergic Receptor Kinases


  • Antigens, CD
  • CCR2 protein, human
  • Chemokine CCL2
  • Chemokine CCL5
  • Inositol Phosphates
  • Phosphatidylinositols
  • Receptor, Anaphylatoxin C5a
  • Receptors, CCR2
  • Receptors, Chemokine
  • Receptors, Complement
  • Receptors, Cytokine
  • Receptors, Interleukin
  • Receptors, Interleukin-8A
  • Virulence Factors, Bordetella
  • Cyclic AMP-Dependent Protein Kinases
  • beta-Adrenergic Receptor Kinases
  • GTP-Binding Proteins