Proliferation of human myeloid leukemia cell line associated with the tyrosine-phosphorylation and activation of the proto-oncogene c-kit product.
We investigated the expression, degree of phosphorylation, and activation of the proto-oncogene c-kit product before and after stimulation with the c-kit ligand in a human factor-dependent myeloid leukemia cell line, MO7E. The culture supernatant of the BALB/3T3 fibroblast cell line, which contains the ligand for the murine c-kit product, was found to stimulate proliferation of the MO7E cell line in a dose-dependent manner. The proliferation was significantly inhibited by a tyrosine kinase inhibitor, genistein. An immunoblot technique with a monoclonal antibody specific for phosphotyrosine, showed that there was rapid, dose-dependent tyrosine-phosphorylation of the c-kit product in response to murine c-kit ligand. Furthermore, the murine c-kit ligand increased autokinase activity of the c-kit product in vitro. Similar results were obtained with human stem cell factor (SCF), a recombinant human ligand for the c-kit product. These results suggest that the phosphorylation and activation of the c-kit product are involved in proliferative signals of some human leukemia cells, as well as of normal hematopoietic cells.
Kuriu
A
A
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Ikeda
H
H
Kanakura
Y
Y
Griffin
J D
JD
Druker
B
B
Yagura
H
H
Kitayama
H
H
Ishikawa
J
J
Nishiura
T
T
Kanayama
Y
Y
D015152:Blotting, Northern; D002455:Cell Division; D015870:Gene Expression; D019833:Genistein; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006801:Humans; D007158:Immunologic Techniques; D007529:Isoflavones / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000473:pathology*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D016298:Hematopoietic Cell Growth Factors; D007529:Isoflavones; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019000:Phosphotyrosine; D014443:Tyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit