The Src kinase Lyn is a negative regulator of mast cell proliferation

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Abstract
Previous investigators have reported that deletion of the protein tyrosine kinase Lyn alters mast cell (MC) signaling responses but does not affect or reduces the cytokine-mediated proliferation of mouse bone marrow-derived MC (BMMC) precursors and of mature MC. We observed that Lyn-deficient mice have more peritoneal MC than wild-type (WT) mice. Studies to explore this unexpected result showed that Lyn−/− BM cells expand faster than WT cells in response to interleukin (IL)-3 and stem-cell factor over the 4–5 weeks required to produce a >95% pure population of granular, receptor with high affinity for immunoglobulin E-positive BMMC. Furthermore, differentiated Lyn−/− BMMC continue to proliferate more rapidly than WT BMMC and undergo less apoptosis in response to cytokine withdrawal. Additionally, Lyn−/− BMMC support greater IL-3-mediated phosphorylation of the prosurvival kinase, Akt, and the proliferative kinase, extracellular-regulated kinase 1/2. These results identify Lyn as a negative regulator of murine MC survival and proliferation.
Funding Information
  • NIH (RO1 GM49814, AI051575, DK58066)
  • NIH (NIGMS)
  • NCI (R24 CA88339)
  • University of New Mexico Cancer Research and Treatment Center