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The Src kinase Lyn is a negative regulator of mast cell proliferation
Author(s) -
HernandezHansen Valerie,
Mackay Graham A.,
Lowell Clifford A.,
Wilson Bridget S.,
Oliver Janet M.
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0503224
Subject(s) - lyn , biology , protein kinase b , microbiology and biotechnology , tyrosine kinase , mast cell , src family kinase , cytokine , proto oncogene tyrosine protein kinase src , stem cell factor , cancer research , kinase , tyrosine protein kinase csk , signal transduction , immunology , stem cell , haematopoiesis , sh3 domain
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 bonemarrow‐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.