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Proliferation of human myeloid leukemia cell line associated with the tyrosine-phosphorylation and activation of the proto-oncogene c-kit product

A Kuriu, H Ikeda, Y Kanakura, JD Griffin, B Druker, H Yagura, H Kitayama, J Ishikawa, T Nishiura and Y Kanayama

Second Department of Internal Medicine, Osaka University Medical School, Japan.

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.

Volume 78, Issue 11, pp. 2834-2840, 12/01/1991
Copyright © 1991 by The American Society of Hematology


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