Rapid phosphorylation of a specific 33-kDa protein (p33) associated with growth stimulated by murine and rat IL3 in different IL3-dependent cell lines, and its constitutive expression in a malignant independent clone.
Protein phosphorylation mediated by murine IL3 and other factors has been studied in two different IL3-dependent lines, AC2 and 123. In both lines, responses to rat recombinant IL3 are enhanced or induced by growth in rat spleen lymphocyte conditioned medium. Growth stimulation by murine and rat IL3, by rat lymphokine(s), and by ATP in ATP-responsive cells is closely associated with the rapid (2-4 min) phosphorylation of a 33-kDa protein (p33) in all the cells examined. p33 phosphorylation is not stimulated by another lymphokine, IL4, nor by TPA or calcium ionophore alone, which are unable to stimulate growth by themselves, and is independent of serum. p33 phosphorylation is inhibited by trifluoperazine, an inhibitor of calcium-calmodulin, but is less sensitive to inhibition by H7, an inhibitor of protein kinase c, in AC2 cells. A spontaneous IL3-independent clone of AC2 (AC-) has been isolated. AC- cells are aggressively leukemic, do not produce detectable IL3, but phosphorylate p33 constitutively where it is associated with a particulate cell fraction. It is suggested that p33 is a common intermediate molecule involved in signal transduction by the various ligands which result in growth stimulation and that its constitutive phosphorylation may play a key role in the maintenance of the leukemic state.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism*; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D003208:Concanavalin A; D003470:Culture Media / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology*; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008970:Molecular Weight; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003470:Culture Media; D007377:Interleukin-3; D007378:Interleukins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D003208:Concanavalin A; D015847:Interleukin-4; D000001:Calcimycin; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate