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Chemokine receptor CCR5 functionally couples to inhibitory G proteins and undergoes desensitization.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 1998 Oct 01; Vol. 71 (1), pp. 36-45. - Publication Year :
- 1998
-
Abstract
- Chemokine receptor CCR5 is not only essential for chemotaxis of leukocytes but also has been shown to be a key coreceptor for HIV-1 infection. In the present study, hemagglutinin epitope-tagged human CCR5 receptor was stably expressed in Chinese hamster ovary cells or transiently expressed in NG108-15 cells to investigate CCR5-mediated signaling events. The surface expression of CCR5 was confirmed by flow cytometry analysis. The CCR5 agonist RANTES stimulated [35S]GTPgammaS binding to the cell membranes and induced inhibition on adenylyl cyclase activity in cells expressing CCR5. The effects of RANTES were CCR5 dependent and could be blocked by pertussis toxin. Furthermore, overexpression of Gialpha2 strongly increased both RANTES-dependent G-protein activation and inhibition on adenylyl cyclase in cells cotransfected with CCR5. These data demonstrated directly that activation of CCR5 stimulated membrane-associated inhibitory G proteins and indicated that CCR5 could functionally couple to G-protein subtype Gialpha2. The abilities of CCR5 to activate G protein and to inhibit cellular cAMP accumulation were significantly diminished after a brief prechallenge with RANTES, showing rapid desensitization of the receptor-mediated responsiveness. Prolonged exposure of the cells to RANTES caused significant reduction of surface CCR5 as measured by flow cytometry, indicative of agonist-dependent receptor internalization. Our data thus demonstrated that CCR5 functionally couples to membrane-associated inhibitory G proteins and undergoes agonist-dependent desensitization and internalization.
- Subjects :
- Adenylate Cyclase Toxin
Animals
CHO Cells drug effects
CHO Cells metabolism
Cricetinae
GTP-Binding Protein alpha Subunit, Gi2
GTP-Binding Protein alpha Subunits, Gi-Go drug effects
GTP-Binding Proteins metabolism
Glioma genetics
Glioma metabolism
Guanosine 5'-O-(3-Thiotriphosphate) metabolism
Hemagglutinin Glycoproteins, Influenza Virus immunology
Humans
Hybrid Cells
Neuroblastoma genetics
Neuroblastoma metabolism
Pertussis Toxin
Proto-Oncogene Proteins metabolism
Receptors, CCR5 genetics
Recombinant Proteins genetics
Recombinant Proteins metabolism
Transfection
Virulence Factors, Bordetella pharmacology
Chemokine CCL5 pharmacology
GTP-Binding Protein alpha Subunits, Gi-Go metabolism
Receptors, CCR5 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0730-2312
- Volume :
- 71
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 9736452
- Full Text :
- https://doi.org/10.1002/(sici)1097-4644(19981001)71:1<36::aid-jcb4>3.0.co;2-2