Acute Myeloid Leukemia Research Today is a free monthly online journal that collates and summarizes the latest research about Acute Myeloid Leukemia, including details on aml, symptoms, treatment, information. | ||||||||
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Signal transduction of c-Kit receptor tyrosine kinase in CHRF myeloid leukemia cells.Scholl S, Kirsch C, Böhmer FD, Klinger R Department of Internal Medicine II (Hematology and Oncology), Friedrich Schiller University Jena, Germany. sebastian.scholl@med.uni-jena.de PURPOSE: The tyrosine kinase receptor c-Kit (stem cell factor receptor, CD117) is a potential target for signal transduction therapy in different cancers. In this study we investigated c-Kit in CHRF cells, a megakaryoblastic cell line of Acute Myeloid Leukemia (FAB M7). MATERIALS AND METHODS: We characterized the interactions between c-Kit and PI 3-kinase (p85) after stimulation with SCF (stem cell factor) as well as the regulation of SHP-1 and SHP-2 associated with Kit in this cell line. RESULTS: Stimulation with SCF leads to a significant increase in interaction between Kit and p85 as well as in receptor associated PI 3-kinase activity. Interestingly, using different kinds of substances (AG 1295, CGP 53716) to inhibit the tyrosine kinase activity of c-Kit blocked activation of c-Kit, but the association of p85 still increased after SCF stimulation even when the tyrosine kinase activity of the receptor was completely blocked. In contrast, the other known interaction partners of c-Kit, SHP-1 and SHP-2, exhibited a basal association with c-Kit and no change of the association could be detected after stimulation of CHRF cells with SCF or treatment with the kinase inhibitors. CONCLUSIONS: Therefore, we suggest that association of p85, SHP-1, and SHP-2 to c-Kit in CHRF cells can, at least in part, occur in a c-Kit kinase-activity independent manner. In contrast, the kinase activity of c-Kit is necessary for the activation of receptor-associated PI 3-kinase. Published 1 November 2004 in J Cancer Res Clin Oncol, 130(12): 711-8.
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