The Src kinase Lyn is a negative regulator of mast cell proliferation.
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.
Hernandez-Hansen
Valerie
V
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
Mackay
Graham A
GA
Lowell
Clifford A
CA
Wilson
Bridget S
BS
Oliver
Janet M
JM
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*
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