Inhibition of adenylyl cyclase by alpha chemokines IL-8 and GRO-alpha in Chinese hamster ovary cells expressing R1 and R2 receptors.
Interleukin-8 (IL-8) and growth-related oncogene protein-alpha (GRO-alpha) belong to a family of alpha chemokines. The biologic effects of IL-8 are realized by binding to two seven-transmembrane receptors R1 and R2 and that of GRO-alpha by binding to receptor R2. Chinese hamster ovary (CHO) cells stably expressing R1 and R2 have been used to demonstrate that the ligand-dependent signaling by both receptors is via the inhibition of adenylyl cyclase. This inhibition is pertussis toxin sensitive and could be mediated by G(alpha)i2, which is present in CHO cells. GRO-alpha inhibits adenylyl cyclase exclusively in CHO-R2 cells, and IL-8 inhibits in both CHO-R1 and CHO-R2 cells. The cAMP status in cells is an easy, reliable, quantifiable signal that is amenable to high throughput screening for small molecule analogs.
Shyamala
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Chiron Corporation, Emeryville, California 94608, USA. shyamala@cc.chiron.com
Khoja
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Moghadam
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D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D016466:CHO Cells; D002630:Chemotactic Factors / Q000494:pharmacology*; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019204:GTP-Binding Proteins / Q000032:analysis; D006133:Growth Substances / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology*; D008565:Membrane Proteins / Q000032:analysis; D037342:Pertussis Toxin; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019707:Receptors, Chemokine / Q000032:analysis*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; D006133:Growth Substances; D016209:Interleukin-8; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019707:Receptors, Chemokine; D010566:Virulence Factors, Bordetella; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go