Pertussis toxin inhibits differentiation induced by retinoic acid in a human promyelocytic leukemia cell line HL-60.
HL-60 is induced to differentiate by retinoic acid (RA) to mature granulocyte-like cells. We found that pretreatment of HL-60 with pertussis toxin (PT) inhibited differentiation induced by various concentrations of RA. This inhibition was observed when PT was prior to the addition of RA. PT ADP-ribosylated a 39,000 Da protein of membrane fraction of HL-60 and did not increase an intracellular cyclic adenosine-3':5'-monophosphate level, indicating that Go, a guanine nucleotide-binding protein, involves signal transduction for RA-induced differentiation. However, Go does not appear to be obligatory for the common pathway of induction of HL-60 differentiation, because PT showed a little or no effect on differentiation induced by other inducers such as 1 alpha,25-dihydroxyvitamin D3, tumor necrosis factor, interferon-gamma, lymphotoxin, prostaglandin E2, cholera toxin, and dimethylsulfoxide.
Hemmi
H
H
Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan.
Nakamura
T
T
Goto
Y
Y
Sugamura
K
K
D002454:Cell Differentiation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D037342:Pertussis Toxin; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010566:Virulence Factors, Bordetella; D014212:Tretinoin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins