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

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 prolif-eration of mouse bone marrow-derived MC (BMMC) precursors and of mature MC. We ob-served that Lyn-deficient mice have more perito-neal MC than wild-type (WT) mice. Studies to ex-plore 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. Further-more, differentiated Lyn/ BMMC continue to proliferate more rapidly than WT BMMC and un-dergo less apoptosis in response to cytokine with-drawal. Additionally, Lyn/ BMMC support greater IL-3-mediated phosphorylation of the pro-survival kinase, Akt, and the proliferative kinase, extracellular-regulated kinase 1/2. These results identify Lyn as a negative regulator of murine M