Gs alpha availability to cholera toxin-catalysed ADP-ribosylation is decreased in membranes of retinoic acid-treated leukemic cell lines HL-60 and THP-1. A posttranslational effect.
Retinoic acid (RA) induces HL-60 and THP-1 leukemic cell lines to differentiate into granulocyte-like and monocyte-like cells. Limited data are available concerning the effects of RA on components of the cyclic AMP pathway in human myeloid leukemic cells. We showed previously a decrease in adenylate cyclase activity in the presence of histamine, prostaglandin E1 and forskolin in RA-treated HL-60 cells as compared to untreated cells. We examined the elements of the signal transduction pathway utilized by RA in the human myeloid cell line HL-60 and the human monocytic cell line THP-1. We therefore studied the effect of RA on the activity of the stimulatory G-protein (Gs). We demonstrate that addition of RA to two human myeloid leukemia cell lines, HL-60 and THP-1, does not induce a reduction of the 2 subunit of Gs (Gs alpha) RNA or Gs alpha protein in the plasma membrane but leads to a rapid decrease in the cholera toxin (CTX)-catalysed ADP-ribosylation of Gs alpha. In addition, this effect seems to be specific to RA, since there was no modification in Gs alpha ADP-ribosylation in the membranes of cells treated with dimethyl sulfoxide (DMSO), another inducer of differentiation in HL-60 cells.
de Cremoux
P
P
Pharmacology Laboratory, Paris 7 University, France.
Zimber
A
A
Calvo
F
F
Lanotte
M
M
Mercken
L
L
Abita
J P
JP
D000244:Adenosine Diphosphate / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D046911:Macromolecular Substances; D009243:NAD / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D046911:Macromolecular Substances; D012333:RNA, Messenger; D009243:NAD; D014212:Tretinoin; D000244:Adenosine Diphosphate; D002772:Cholera Toxin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins