Signaling pathways activated in a unique mast cell line where interleukin-3 supports survival and stem cell factor is required for a proliferative response.
Stem cell factor (SCF) and interleukin-3 (IL-3) both act on several target hematopoietic populations, including mast cells. We have isolated a unique murine mast cell line, B6M, that is phenotypically similar to immature mast cells. For B6M cells, IL-3 is a survival factor and alone does not stimulate proliferation. SCF can stimulate proliferation of B6M cells, and together IL-3 and SCF synergize to stimulate optimal proliferation and long-term growth. A sustained induction of c-myc is observed only in the presence of SCF (with or without IL-3). In B6M cells, both IL-3 and SCF stimulate phosphorylation of Shc and activation of the Ras, Raf-1, MAPK pathway. Interestingly, IL-3 plus SCF synergistically activate MAPK. IL-3, but not SCF, leads to activation of Jak 2 and Stat 5 and induces pim-1 expression. From these data, we suggest that the induction of pim-1 and c-myc is independently regulated. Furthermore, IL-3-stimulated activation of the Jak 2/Stat 5 pathway, induction of pim-1, and activation of the Ras/MAPK pathway are insufficient to mediate proliferation of B6M cells. The unusual IL-3 response of B6M cells provides a useful model to dissect signals required for IL-3-stimulated survival and proliferation.
O'Farrell
A M
AM
Department of Cell Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.
Ichihara
M
M
Mui
A L
AL
Miyajima
A
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D007377:Interleukin-3 / Q000494:pharmacology*; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000494:pharmacology*
D007377:Interleukin-3; D019089:Stem Cell Factor