This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Honda, Z.-i.
Right arrow Articles by Yamamoto, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Honda, Z.-i.
Right arrow Articles by Yamamoto, K.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2000, p. 1759-1771, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Sequential Requirements of the N-Terminal Palmitoylation Site and SH2 Domain of Src Family Kinases in the Initiation and Progression of Fcepsilon RI Signaling

Zen-ichiro Honda,1,* Takeshi Suzuki,1 Hajime Kono,1 Masato Okada,2 Tadashi Yamamoto,3 Chisei Ra,4 Yutaka Morita,1 and Kazuhiko Yamamoto1

Department of Allergy and Rheumatology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655,1 Division of Protein Metabolism, Institute of Protein Research, Osaka University, Suita, Osaka,2 Institute of Medical Science, University of Tolyo, Shirokanedai, Minato-ku, Tokyo,3 and Department of Immunology, School of Medicine, Juntendo University, Bunkyo-ku Tokyo 113-8421,4 Japan

Received 7 June 1999/Returned for modification 8 July 1999/Accepted 10 November 1999

Initial biochemical signaling originating from high-affinity immunoglobulin E receptor (Fcvarepsilon RI) has been ascribed to Src family kinases. To understand the mechanisms by which individual kinases drive the signaling, we conducted reconstitution experiments: Fcvarepsilon RI signaling in RBL2H3 cells was first suppressed by a membrane-anchored, gain-of-function C-terminal Src kinase and then reconstructed with Src family kinases whose C-terminal negative regulatory sequence was replaced with a c-myc epitope. Those constructs derived from Lyn and Fyn, which are associated with detergent-resistant membranes (DRMs), physically interacted with resting Fcvarepsilon RI and reconstructed clustering-induced signaling that leads to calcium mobilization and ERK1 and -2 activation. c-Src-derived construct, which was excluded from DRMs, failed to interact with Fcvarepsilon RI and to restore the signaling, whereas creation of palmitoylatable Cys3 enabled it to interact with DRMs and with Fcvarepsilon RI and to restore the signaling. Deletion of Src homology 3 (SH3) domain from the Lyn-derived construct did not alter its ability to transduce the series of signaling. Deletion of SH2 domain did not affect its association with DRMs and with Fcvarepsilon RI nor clustering-induced tyrosine phosphorylation of Fcvarepsilon RI beta  and gamma  subunits, but it almost abrogated the next step of tyrosine phosphorylation of Syk and its recruitment to Fcvarepsilon RI. These findings suggest that Lyn and Fyn could, but c-Src could not, drive Fcvarepsilon RI signaling and that N-terminal palmitoylation and SH2 domain are required in sequence for the initial interaction with Fcvarepsilon RI and for the signal progression to the molecular assembly.

* Corresponding author. Mailing address: Department of Allergy and Rheumatology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Phone: 3-3815-5411. Fax: 3-3815-5954. E-mail: honda-phy{at}h.u-tokyo.ac.jp.

Molecular and Cellular Biology, March 2000, p. 1759-1771, Vol. 20, No. 5
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Draper, J. M., Xia, Z., Smith, C. D. (2007). Cellular palmitoylation and trafficking of lipidated peptides. J. Lipid Res. 48: 1873-1884 [Abstract] [Full Text]  
  • Resh, M. D. (2006). Palmitoylation of Ligands, Receptors, and Intracellular Signaling Molecules. Sci Signal 2006: re14-re14 [Abstract] [Full Text]  
  • Larson, D. R., Gosse, J. A., Holowka, D. A., Baird, B. A., Webb, W. W. (2005). Temporally resolved interactions between antigen-stimulated IgE receptors and Lyn kinase on living cells. JCB 171: 527-536 [Abstract] [Full Text]  
  • Kono, H., Kyogoku, C., Suzuki, T., Tsuchiya, N., Honda, H., Yamamoto, K., Tokunaga, K., Honda, Z.-I. (2005). Fc{gamma}RIIB Ile232Thr transmembrane polymorphism associated with human systemic lupus erythematosus decreases affinity to lipid rafts and attenuates inhibitory effects on B cell receptor signaling. Hum Mol Genet 14: 2881-2892 [Abstract] [Full Text]  
  • Epling-Burnette, P. K., Painter, J. S., Chaurasia, P., Bai, F., Wei, S., Djeu, J. Y., Loughran, T. P. Jr (2004). Dysregulated NK receptor expression in patients with lymphoproliferative disease of granular lymphocytes. Blood 103: 3431-3439 [Abstract] [Full Text]  
  • Qu, X., Sada, K., Kyo, S., Maeno, K., Miah, S. M. S., Yamamura, H. (2004). Negative regulation of Fc{epsilon}RI-mediated mast cell activation by a ubiquitin-protein ligase Cbl-b. Blood 103: 1779-1786 [Abstract] [Full Text]  
  • Young, R. M., Holowka, D., Baird, B. (2003). A Lipid Raft Environment Enhances Lyn Kinase Activity by Protecting the Active Site Tyrosine from Dephosphorylation. J. Biol. Chem. 278: 20746-20752 [Abstract] [Full Text]  
  • Faeder, J. R., Hlavacek, W. S., Reischl, I., Blinov, M. L., Metzger, H., Redondo, A., Wofsy, C., Goldstein, B. (2003). Investigation of Early Events in Fc{epsilon}RI-Mediated Signaling Using a Detailed Mathematical Model. J. Immunol. 170: 3769-3781 [Abstract] [Full Text]  
  • Sada, K., Miah, S. M. S., Maeno, K., Kyo, S., Qu, X., Yamamura, H. (2002). Regulation of Fcepsilon RI-mediated degranulation by an adaptor protein 3BP2 in rat basophilic leukemia RBL-2H3 cells. Blood 100: 2138-2144 [Abstract] [Full Text]  
  • Kono, H., Suzuki, T., Yamamoto, K., Okada, M., Yamamoto, T., Honda, Z.-i. (2002). Spatial Raft Coalescence Represents an Initial Step in Fc{gamma}R Signaling. J. Immunol. 169: 193-203 [Abstract] [Full Text]  
  • Tolar, P., Arudchandran, R., Draberova, L., Rivera, J., Draber, P. (2001). Structure-Function Analysis of Lyn Kinase Association with Lipid Rafts and Initiation of Early Signaling Events after Fcvarepsilon Receptor I Aggregation. Mol. Cell. Biol. 21: 8318-8328 [Abstract] [Full Text]  
  • Sada, K., Zhang, J., Siraganian, R. P. (2001). SH2 domain-mediated targeting, but not localization, of Syk in the plasma membrane is critical for Fc{epsilon}RI signaling. Blood 97: 1352-1359 [Abstract] [Full Text]  
  • Quek, L. S., Pasquet, J.-M., Hers, I., Cornall, R., Knight, G., Barnes, M., Hibbs, M. L., Dunn, A. R., Lowell, C. A., Watson, S. P. (2000). Fyn and Lyn phosphorylate the Fc receptor gamma chain downstream of glycoprotein VI in murine platelets, and Lyn regulates a novel feedback pathway. Blood 96: 4246-4253 [Abstract] [Full Text]  
  • Suzuki, T., Kono, H., Hirose, N., Okada, M., Yamamoto, T., Yamamoto, K., Honda, Z.-i. (2000). Differential Involvement of Src Family Kinases in Fc{gamma} Receptor-Mediated Phagocytosis. J. Immunol. 165: 473-482 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»