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Blood, 1 July 2004, Vol. 104, No. 1, pp. 207-214. Prepublished online as a Blood First Edition Paper on March 9, 2004; DOI 10.1182/blood-2003-08-2769. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-08-2769v1 104/1/207    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tkaczyk, C. Articles by Gilfillan, A. M. Search for Related Content PubMed PubMed Citation Articles by Tkaczyk, C. Articles by Gilfillan, A. M. Related Collections Signal Transduction Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY NTAL phosphorylation is a pivotal link between the signaling cascades leading to human mast cell degranulation following Kit activation and FcRI aggregation Christine Tkaczyk, Vaclav Horejsi, Shoko Iwaki, Petr Draber, Lawrence E. Samelson, Anne B. Satterthwaite, Dong-Ho Nahm, Dean D. Metcalfe, and Alasdair M. Gilfillan From the Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD; the Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic; the Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda MD; and the Department of Internal Medicine and Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX. Aggregation of high-affinity receptors for immunoglobulin E (FcRI) on the surface of mast cells results in degranulation, a response that is potentiated by binding of stem cell factor (SCF) to its receptor Kit. We observed that one of the major initial signaling events associated with FcRI-mediated activation of human mast cells (HuMCs) is the rapid tyrosine phosphorylation of a protein of 25 to 30 kDa. The phosphorylation of this protein was also observed in response to SCF. This protein was identified as non–T-cell activation linker (NTAL), an adaptor molecule similar to linker for activated T cells (LAT). Unlike the FcRI response, SCF induced NTAL phosphorylation in the absence of detectable LAT phosphorylation. When SCF and antigen were added concurrently, there was a marked synergistic effect on NTAL phosphorylation, however, SCF did not enhance the phosphorylation of LAT induced by FcRI aggregation. FcRI- and SCF-mediated NTAL phosphorylation appear to be differentially regulated by Src kinases and/or Kit kinase, respectively. Diminution of NTAL expression by silencing RNA oligonucleotides in HuMCs resulted in a reduction of both Kit- and FcRI-mediated degranulation. NTAL, thus, appears to be an important link between the signaling pathways that are initiated by these receptors, culminating in mast cell degranulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Bachelet, A. Munitz, B. Berent-Maoz, D. Mankuta, and F. Levi-Schaffer Suppression of Normal and Malignant Kit Signaling by a Bispecific Antibody Linking Kit with CD300a J. Immunol., May 1, 2008; 180(9): 6064 - 6069. [Abstract] [Full Text] [PDF] M.-S. Kim, H. S. Kuehn, D. D. Metcalfe, and A. M. Gilfillan Activation and Function of the mTORC1 Pathway in Mast Cells J. Immunol., April 1, 2008; 180(7): 4586 - 4595. [Abstract] [Full Text] [PDF] K. Roget, M. Malissen, O. Malbec, B. Malissen, and M. Daeron Non-T Cell Activation Linker Promotes Mast Cell Survival by Dampening the Recruitment of SHIP1 by Linker for Activation of T Cells J. Immunol., March 15, 2008; 180(6): 3689 - 3698. [Abstract] [Full Text] [PDF] B. M. Jensen, M. A. Beaven, S. Iwaki, D. D. Metcalfe, and A. M. 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Saito LAT and NTAL Mediate Immunoglobulin E-Induced Sustained Extracellular Signal-Regulated Kinase Activation Critical for Mast Cell Survival Mol. Cell. Biol., June 15, 2007; 27(12): 4406 - 4415. [Abstract] [Full Text] [PDF] A. S. Tessarz, S. Weiler, K. Zanzinger, P. Angelisova, V. Horejsi, and A. Cerwenka Non-T Cell Activation Linker (NTAL) Negatively Regulates TREM-1/DAP12-Induced Inflammatory Cytokine Production in Myeloid Cells J. Immunol., February 15, 2007; 178(4): 1991 - 1999. [Abstract] [Full Text] [PDF] N. M. Kushnir-Sukhov, A. M. Gilfillan, J. W. Coleman, J. M. Brown, S. Bruening, M. Toth, and D. D. Metcalfe 5-Hydroxytryptamine Induces Mast Cell Adhesion and Migration J. Immunol., November 1, 2006; 177(9): 6422 - 6432. [Abstract] [Full Text] [PDF] S. Iwaki, C. Tkaczyk, A. B. Satterthwaite, K. Halcomb, M. A. Beaven, D. D. Metcalfe, and A. M. Gilfillan Btk Plays a Crucial Role in the Amplification of Fc{epsilon}RI-mediated Mast Cell Activation by Kit J. Biol. 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