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

• Published in: FEBS letters 2004-07, Vol.570 (1-3), p.126-132
• Main Authors: Mueller, Anja, Strange, Philip G
• Format: Article
• Language: English
• Subjects: [35S]GTPγS binding assay; Animals; Blotting, Western; Calcium - metabolism; Calcium ion release; CCR5; Chemokine CCL3; Chemokine CCL4; Chemokine CCL5; Chemokines, CC - metabolism; CHO Cells; CHO cells, Chinese hamster ovary cells; Cricetinae; Electrophoresis, Polyacrylamide Gel; FCS, foetal calf serum; FITC, fluorescein isothiocyanate; Flow Cytometry; G protein; GPCR, G protein coupled receptor; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; HEK cells, human embryonic kidney cells; HIV, human immunodeficiency virus; IP, immunoprecipitation; JAK, Janus kinase; JAK2; Janus Kinase 2; Ligands; Macrophage Inflammatory Proteins - metabolism; PBS, phosphate-buffered saline; Pertussis Toxin - pharmacology; Phosphorylation; Precipitin Tests; Protein Binding; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins; PTX, pertussis toxin; STAT, signal transducer and activator of transcription; Time Factors; Tyrphostins - pharmacology
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2004.04.100

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.