Signaling pathways influencing SLF and c-kit-mediated survival and proliferation.
Steel factor (SLF) and c-Kit are a ligand-receptor pair that regulates growth and activation of a variety of hemopoietic and non-hemopoietic cells. This review describes our work investigating downstream signaling pathways activated by SLF, with particular emphasis on signaling differences associated with soluble vs membrane- bound ligand, and our identification of an important role for PLC activation and Ca2+ influx in supporting c-Kit positive cells in vitro and in vivo. This work led to the identification of a unique form of cell death termed activation enhanced cell death (AECD) that involves stimulating a cell with a growth or activation signal while concurrently blocking Ca2+ influx. Approaches that we have taken toward identifying cellular factors associated with sensitivity and resistance to AECD are summarized, as is our experience with a variety of experimental models. The use of econazole as a calcium channel blocker and its mechanism of action are described, as is its potential for development as an anticancer therapeutic.
Berger
Stuart A
SA
The Arthritis and Immune Disorder Research Centre, University Health Network and the Department of Immunology, University of Toronto, Toronto, Ontario, Canada. Berger@uhnres.utoronto.ca
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D051379:Mice; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism* / Q000494:pharmacology
D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit