title: Alterations in tyrosine phosphorylation during the granulocytic maturation of HL-60 leukemia cells.
abstract: Granulocytic maturation of HL-60 promyelocytic leukemia cells induced by dimethylsulfoxide has been shown to produce a decrease in cellular protein phosphotyrosine residues and increases in both tyrosine kinase and protein phosphotyrosine phosphatase activities (D. A. Frank and A. C. Sartorelli, Biochem. Biophys. Res. Commun., 140: 440-447, 1986). These changes have been shown to not be restricted to dimethylsulfoxide-induced differentiation, since similar changes occur in HL-60 cells initiated with retinoic acid and in HL-60 sublines resistant to dimethylsulfoxide-induced differentiation treated with the retinoid. These regulatory events are not directly coupled to growth arrest, which accompanies terminal maturation, since the anthracycline antibiotics aclacinomycin A and marcellomycin, which induce HL-60 differentiation, cause these changes in phosphotyrosine metabolism, while Adriamycin, at a level which produces an equivalent degree of growth inhibition but does not initiate the maturation of HL-60 cells, does not. Furthermore, an HL-60 subline deficient in hypoxanthine-guanine phosphoribosyltransferase, which differentiates in the presence of 6-thioguanine, produced a decrease in phosphotyrosine residues and increases in tyrosine kinase and phosphotyrosine phosphatase activities in response to the purine antimetabolite, while the parental HL-60 line, in which 6-thioguanine inhibits cellular proliferation but does not induce maturation, does not exhibit these changes. Finally, similar alterations in phosphotyrosine regulation were exhibited during anthracycline-induced differentiation of the murine myelomonocytic leukemia cell line WEHI-3B D+, supporting the concept that the phenomena measured represent a general response to inducers of the granulocytic differentiation of leukemia cells.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: D A
authors.initials: DA
authors.lastname: Frank
authors.forename: A C
authors.initials: AC
authors.lastname: Sartorelli
mesh_terms: D015250:Aclarubicin; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D002454:Cell Differentiation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D009279:Naphthacenes / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000032:analysis; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D013866:Thioguanine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; C015338:marcellomycin; D014443:Tyrosine; D015250:Aclarubicin; D011505:Protein-Tyrosine Kinases; D010749:Phosphoprotein Phosphatases; D017027:Protein Tyrosine Phosphatases; D013866:Thioguanine; D004121:Dimethyl Sulfoxide