Abstract
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). 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. 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. Therefore, we suggest that association of p85, SHP-1, and SHP-2 to c-Kit in CHRF cells can, at l...Continue Reading
References
Aug 7, 1992·Cell·I D HilesN F Totty
Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·M Z RatajczakA M Gewirtz
Oct 30, 1992·Cell·T Pawson, G D Gish
Apr 20, 1990·Cell·A Ullrich, J Schlessinger
Aug 4, 1995·Science·B StoyanovB Nürnberg
Jun 1, 1993·Molecular and Cellular Biology·T Yi, J N Ihle
Mar 10, 1995·Cell·U KlingmüllerH F Lodish
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·P PeraldiE Van Obberghen
Oct 15, 1993·Biochemical and Biophysical Research Communications·L BastienM Adam
Dec 1, 1993·Molecular and Cellular Biology·P HuJ Schlessinger
Oct 1, 1995·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·H T Hassan, M Freund
Feb 16, 1996·The Journal of Biological Chemistry·M Kon-KozlowskiK A Siminovitch
Apr 1, 1996·In Vitro Cellular & Developmental Biology. Animal·B SandrockM A Lieberman
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·B VanhaesebroeckM D Waterfield
Apr 7, 1998·Molecular and Cellular Biology·M KozlowskiK A Siminovitch
Apr 5, 2001·The New England Journal of Medicine·B J DrukerC L Sawyers
Sep 6, 2001·Blood·P D KottaridisD C Linch
Apr 24, 2002·Oncogene·Hitoshi KiyoiTomoki Naoe
Feb 26, 2003·Drugs·Katherine F Croom, Caroline M Perry
Jul 1, 1993·Current Biology : CB·T Pawson, J Schlessingert
Citations
Apr 18, 2013·PloS One·Jean-Baptiste BachetLaurent Alberti
Mar 17, 2009·Biochemical and Biophysical Research Communications·Lian LiuChunhong Ma
Oct 20, 2018·Oncology Letters·Xiaowei XieLingyun Ma