Reduction of adenylyl cyclase activity by cholera toxin in myeloid cells. Long-term down-regulation of Gs alpha subunits by cholera toxin treatment.
In IPC-81 cells, the adenylyl-cyclase activation by cholera toxin produces an elevation of cAMP that causes a rapid cytolysis. A resistant clone with deficient cholera toxin-induced cyclase activity (yet sensitive to cAMP) showed a rapid decrease in the amount of membrane-bound Gs alpha (42-47 kDa) detectable soon after ADP-ribosylation of these proteins; pertussis toxin-sensitive G proteins (41 kDa) were not affected. Resistant cells showed a rapid decrease of Gs alpha that is consistent with the finding that cAMP did not accumulate in these cells. Cholera toxin treatment of resistant cells had long-lasting effects (several weeks) on the level of Gs alpha in the cell membrane. The duration of Gs alpha decrease does not correspond to the probable life of catalytically active cholera toxin in the cells, and suggests a regulated process more complex than a proteolytic degradation targeted on ADP-ribosylated molecules.
Hermouet
S
S
INSERM U301, Hôpital Saint-Louis, Paris, France.
Milligan
G
G
Lanotte
M
M
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000096:biosynthesis; D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D002772:Cholera Toxin / Q000494:pharmacology*; D004351:Drug Resistance; D004789:Enzyme Activation / Q000187:drug effects; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D015151:Immunoblotting; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology; D008565:Membrane Proteins / Q000378:metabolism; D037342:Pertussis Toxin; D051381:Rats; D013873:Thionucleotides / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D008565:Membrane Proteins; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; C034882:guanosine 5'-O-(1-thiotriphosphate); D000246:Adenosine Diphosphate Ribose; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D002772:Cholera Toxin; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases