title: 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 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.
authors.affiliation: Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, CRF Rm. 205, 2325 Camino De Salud NE, Albuquerque, NM 87131, USA. valh@unm.edu
authors.forename: Valerie
authors.initials: V
authors.lastname: Hernandez-Hansen
authors.forename: Graham A
authors.initials: GA
authors.lastname: Mackay
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lowell
authors.forename: Bridget S
authors.initials: BS
authors.lastname: Wilson
authors.forename: Janet M
authors.initials: JM
authors.lastname: Oliver
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D006133:Growth Substances; D007377:Interleukin-3; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases