Btk Plays a Crucial Role in the Amplification of FcϵRI-mediated Mast Cell Activation by Kit

作者: Shoko Iwaki , Christine Tkaczyk , Anne B. Satterthwaite , Kristina Halcomb , Michael A. Beaven

DOI: 10.1074/JBC.M506063200

关键词:

摘要: Stem cell factor (SCF) acts in synergy with antigen to enhance the calcium signal, degranulation, activation of transcription factors, and cytokine production human mast cells. However, underlying mechanisms for this remain unclear. Here we show, utilizing bone marrow-derived cells (BMMCs) from Btk Lyn knock-out mice, that via plays a key role promoting synergy. As cells, SCF enhanced degranulation BMMCs. In Btk-/- BMMCs, which there was partial reduction capacity degranulate response antigen, unable residual antigen-mediated degranulation. Furthermore, as ability promote abrogated The impairment responses correlated an inability augment phospholipase Cγ1 mobilization, phosphorylate NFκB NFAT gene these Similar studies Lyn-/- Btk-/-/Lyn-/- BMMCs indicated regulator responses. These data demonstrate, first time, is Kit-mediated amplification pathway augments FcϵRI-mediated activation.

参考文章(50)
CJ Meininger, H Yano, R Rottapel, A Bernstein, KM Zsebo, BR Zetter, The c-kit receptor ligand functions as a mast cell chemoattractant. Blood. ,vol. 79, pp. 958- 963 ,(1992) , 10.1182/BLOOD.V79.4.958.958
Mindy Tsai, Stephen J. Galli, Akikazu Ando, Akihiro Iemura, Barry K. Wershil, The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis. American Journal of Pathology. ,vol. 144, pp. 321- 328 ,(1994)
Mindy Tsai, Stephen J. Galli, Barry K. Wershil, The c-kit receptor, stem cell factor, and mast cells. What each is teaching us about the others. American Journal of Pathology. ,vol. 142, pp. 965- 974 ,(1993)
Nadine Varin-Blank, Anne Weyer, Juan Rivera, Françoise Marchand, Bernard David, Claire Pelletier, Ulrich Blank, Bruno Iannascoli, FcεRI-Mediated Induction of TNF-α Gene Expression in the RBL-2H3 Mast Cell Line: Regulation by a Novel NF-κB-Like Nuclear Binding Complex Journal of Immunology. ,vol. 161, pp. 4768- 4776 ,(1998)
M.H. Jouvin, M. Adamczewski, R. Numerof, O. Letourneur, A. Vallé, J.P. Kinet, Differential control of the tyrosine kinases Lyn and Syk by the two signaling chains of the high affinity immunoglobulin E receptor. Journal of Biological Chemistry. ,vol. 269, pp. 5918- 5925 ,(1994) , 10.1016/S0021-9258(17)37549-X
Yuko Kawakami, Jiro Kitaura, Anne B. Satterthwaite, Roberta M. Kato, Koichi Asai, Stephen E. Hartman, Mari Maeda-Yamamoto, Clifford A. Lowell, David J. Rawlings, Owen N. Witte, Toshiaki Kawakami, Redundant and Opposing Functions of Two Tyrosine Kinases, Btk and Lyn, in Mast Cell Activation The Journal of Immunology. ,vol. 165, pp. 1210- 1219 ,(2000) , 10.4049/JIMMUNOL.165.3.1210
William R. Coward, Yoshimichi Okayama, Hironori Sagara, Susan J. Wilson, Stephen T. Holgate, Martin K. Church, NF-κB and TNF-α: A Positive Autocrine Loop in Human Lung Mast Cells? Journal of Immunology. ,vol. 169, pp. 5287- 5293 ,(2002) , 10.4049/JIMMUNOL.169.9.5287