Modulation of monocytic differentiation of HL-60 cells by inhibitors of protein tyrosine kinases.
We showed previously that the expressions of various src family protein tyrosine kinases (PTKs) were induced independently during the monocytic differentiation of HL-60 cells. The role of PTKs was further assessed in the present study by investigating the effects of PTK inhibitors on the differentiation. It was demonstrated that PTK inhibitors such as genistein and herbimycin A modulated monocytic differentiation of HL-60 cells; they inhibited the differentiation induced by TPA, while promoting that induced by vitamin D3 (D3). Immunoblotting analysis of protein molecules which had been phosphorylated on their tyrosine residues demonstrated that TPA induced phosphorylation of certain molecules different from those induced by D3 in HL-60 cells. PTK inhibitors blocked the phosphorylation and modulated differentiation driven by the inducers. These data suggest that PTKs are involved both promotively and suppressively in signaling events that induce monocytic differentiation of HL-60 cells.
Katagiri
K
K
Tokyo Institute for Immunopharmacology, Inc., Japan.
Katagiri
T
T
Kajiyama
K
K
Uehara
Y
Y
Yamamoto
T
T
Yoshida
T
T
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D016227:Benzoquinones; D002454:Cell Differentiation / Q000187:drug effects*; D002762:Cholecalciferol / Q000494:pharmacology; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D011809:Quinones; D002762:Cholecalciferol; D017828:Rifabutin; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate