The unique signalling requirements of c-Kit§+ cells stimulated by membrane-bound Steel Factor

grantor: University of TorontoSignalling requirements for PI3-kinase and PLC-ã following stimulation of c-Kit+ cells by either soluble Steel Factor or membrane-bound Steel Factor were examined. By studying 32D-KitYF728 and YF719 cells, it was found that PLC-ã activation is required for stimulation by membrane-bound Steel Factor. Stimulation by membrane-bound Steel Factor of 32D cells expressing a wild-type c-Kit receptor was inhibited by neomycin sulfate. Stimulation of bone marrow-derived mast cells by mSLF was inhibited by neomycin sulfate and oleic acid. A study of both antagonists revealed that neither inhibits c-Kit or PLC-ã phosphorylation. PI3-kinase is recruited to the c-Kit receptor following mSLF stimulation of murine bone marrow-derived mast cells. To test the efficacy of the PLC antagonists 'in vivo', the effects of neomycin sulfate and oleic acid were studied in mice. Oleic acid, but not neomycin sulfate, has some potential for reducing overall skin mast cell numbers without visibly affecting surrounding tissue.M.Sc