Published online before print October 2, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque; and
Department of Laboratory Medicine, University of California, San Francisco
1Correspondence: Department of Pathology, University of New Mexico School of Medicine, CRF Rm. 205, 2325 Camino De Salud NE, Albuquerque, NM 87131. E-mail: valh{at}unm.edu
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.
Key Words: mast cells/basophils • signal transduction • apoptosis • cellular proliferation • cellular activation
This article has been cited by other articles:
 |
|
 |
|
  H.-J. Kim, K. Zhang, L. Zhang, F. P. Ross, S. L. Teitelbaum, and R. Faccio The Src family kinase, Lyn, suppresses osteoclastogenesis in vitro and in vivo PNAS, February 17, 2009; 106(7): 2325 - 2330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Simon, E. Dondi, A. Chaix, P. de Sepulveda, T. J. Kubiseski, N. Varin-Blank, and L. Velazquez Lnk adaptor protein down-regulates specific Kit-induced signaling pathways in primary mast cells Blood, November 15, 2008; 112(10): 4039 - 4047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Samayawardhena and C. J. Pallen Protein-tyrosine Phosphatase {alpha} Regulates Stem Cell Factor-dependent c-Kit Activation and Migration of Mast Cells J. Biol. Chem., October 24, 2008; 283(43): 29175 - 29185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Iyer and A. August The Tec Family Kinase, IL-2-Inducible T Cell Kinase, Differentially Controls Mast Cell Responses J. Immunol., June 15, 2008; 180(12): 7869 - 7877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kennedy Norton, B. Barnstein, J. Brenzovich, D. P. Bailey, M. Kashyap, K. Speiran, J. Ford, D. Conrad, S. Watowich, M. R. Moralle, et al. IL-10 Suppresses Mast Cell IgE Receptor Expression and Signaling In Vitro and In Vivo J. Immunol., March 1, 2008; 180(5): 2848 - 2854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hong, J. Kitaura, W. Xiao, V. Horejsi, C. Ra, C. A. Lowell, Y. Kawakami, and T. Kawakami The Src family kinase Hck regulates mast cell activation by suppressing an inhibitory Src family kinase Lyn Blood, October 1, 2007; 110(7): 2511 - 2519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kitaura, Y. Kawakami, M. Maeda-Yamamoto, V. Horejsi, and T. Kawakami Dysregulation of Src Family Kinases in Mast Cells from Epilepsy-Resistant ASK versus Epilepsy-Prone EL Mice J. Immunol., January 1, 2007; 178(1): 455 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Mermel, M. L. McLemore, F. Liu, S. Pereira, J. Woloszynek, C. A. Lowell, and D. C. Link Src family kinases are important negative regulators of G-CSF-dependent granulopoiesis Blood, October 15, 2006; 108(8): 2562 - 2568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. G. Karur, C. A. Lowell, P. Besmer, V. Agosti, and D. M. Wojchowski Lyn kinase promotes erythroblast expansion and late-stage development Blood, September 1, 2006; 108(5): 1524 - 1532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yu, C. A. Lowell, B. G. Neel, and H. Gu Scaffolding Adapter Grb2-Associated Binder 2 Requires Syk to Transmit Signals from Fc{epsilon}RI J. Immunol., February 15, 2006; 176(4): 2421 - 2429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Hernandez-Hansen, J. D. J. Bard, C. A. Tarleton, J. A. Wilder, C. A. Lowell, B. S. Wilson, and J. M. Oliver Increased Expression of Genes Linked to Fc{epsilon}RI Signaling and to Cytokine and Chemokine Production in Lyn-Deficient Mast Cells J. Immunol., December 15, 2005; 175(12): 7880 - 7888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-L. Chu and C. A. Lowell The Lyn Tyrosine Kinase Differentially Regulates Dendritic Cell Generation and Maturation J. Immunol., September 1, 2005; 175(5): 2880 - 2889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Harder, C. Quilici, E. Naik, M. Inglese, N. Kountouri, A. Turner, K. Zlatic, D. M. Tarlinton, and M. L. Hibbs Perturbed myelo/erythropoiesis in Lyn-deficient mice is similar to that in mice lacking the inhibitory phosphatases SHP-1 and SHIP-1 Blood, December 15, 2004; 104(13): 3901 - 3910. [Abstract] [Full Text] [PDF]
|
|
