CCL3, acting via the chemokine receptor CCR5, leads to independent activation of Janus kinase 2 (JAK2) and Gi proteins

FEBS Lett. 2004 Jul 16;570(1-3):126-32. doi: 10.1016/j.febslet.2004.04.100.

Abstract

The interaction of the chemokine receptor, CCR5, expressed in recombinant cells, with different G proteins was investigated and CCR5 was found to interact with Gi, Go and Gq species. Interaction with Gi leads to G protein activation, whereas Gq does not seem to be activated. Additionally, CCR5 activation also leads to phosphorylation of Janus kinase 2 (JAK2). Activation of JAK2 is independent of Gi or Gq activation. Gi protein activation was not prevented by inhibition of JAK, showing that heterotrimeric G protein activation and activation of the JAK/signal transducer and activator of transcription (STAT) pathway are independent of each other.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • CHO Cells
  • Calcium / metabolism
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines, CC / metabolism*
  • Cricetinae
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
  • GTP-Binding Proteins
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Janus Kinase 2
  • Ligands
  • Macrophage Inflammatory Proteins / metabolism*
  • Pertussis Toxin / pharmacology
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins*
  • Time Factors
  • Tyrphostins / pharmacology

Substances

  • CCL5 protein, human
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokines, CC
  • Ligands
  • Macrophage Inflammatory Proteins
  • Proto-Oncogene Proteins
  • Tyrphostins
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Pertussis Toxin
  • Protein-Tyrosine Kinases
  • JAK2 protein, human
  • Janus Kinase 2
  • GTP-Binding Proteins
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • Calcium