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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2410-2417. Prepublished online as a Blood First Edition Paper on June 24, 2004; DOI 10.1182/blood-2004-02-0631. This Article Full Text (PDF) All Versions of this Article: 2004-02-0631v1 104/8/2410    most recent Alert me when this article is cited Alert me if a correction is posted 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 Hundley, T. R Articles by Beaven, M. A Search for Related Content PubMed PubMed Citation Articles by Hundley, T. R Articles by Beaven, M. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 19, 2004 Accepted May 25, 2004 Kit and FcRI Mediate Unique and Convergent Signals for Release of Inflammatory Mediators from Human Mast Cells Thomas R Hundley, Alasdair M Gilfillan, Christine Tkaczyk, Marcus V Andrade, Dean D Metcalfe, and Michael A Beaven* Laboratory of Molecular Immunology, National, Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA * Corresponding author; email: beaven{at}helix.nih.gov. In human mast cells, derived from CD34+ peripheral blood cells, we observed that Kit ligand (KL) failed to induce degranulation but acted in synergy with antigen to markedly enhance degranulation, levels of cytokine gene transcripts, and production of cytokines. Further examination revealed that antigen and KL activated common and unique signaling pathways to account for these varied responses. KL, unlike antigen, failed to activate protein kinase C but activated phospholipase C and calcium mobilization and augmented these signals as well as degranulation when added together with antigen. Both KL and antigen induced signals that are associated with cytokine production namely, phosphorylation of the mitogen-activated protein kinases, phosphatidylinositol 3-kinase-dependent phosphorylation of Akt, and phosphorylation of NFB. However, only KL stimulated phosphorylation of STAT5 and STAT6 while antigen weakly stimulated the protein kinase C-dependent induction and phosphorylation of c-Jun and associated AP-1 components, an action that was markedly potentiated by co-stimulation with KL. Interestingly, most signals were down-regulated on continuous exposure to KL but were reactivated along with gene transcription on addition of antigen. The findings, in total, indicated that a combination of FcRI and Kit mediated signals and transcriptional processes were required for optimal physiologic responses of human mast cells to antigen. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] B. M. Jensen, M. A. Beaven, S. Iwaki, D. D. Metcalfe, and A. M. Gilfillan Concurrent Inhibition of Kit- and Fc{epsilon}RI-Mediated Signaling: Coordinated Suppression of Mast Cell Activation J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 128 - 138. [Abstract] [Full Text] [PDF] C. Akin, L. M. Scott, C. N. Kocabas, N. Kushnir-Sukhov, E. Brittain, P. Noel, and D. D. 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Bachelet, A. Munitz, D. Mankutad, and F. Levi-Schaffer Mast Cell Costimulation by CD226/CD112 (DNAM-1/Nectin-2): A NOVEL INTERFACE IN THE ALLERGIC PROCESS J. Biol. Chem., September 15, 2006; 281(37): 27190 - 27196. [Abstract] [Full Text] [PDF] B. O. Barnstein, G. Li, Z. Wang, S. Kennedy, C. Chalfant, H. Nakajima, K. D. Bunting, and J. J. Ryan Stat5 Expression Is Required for IgE-Mediated Mast Cell Function. J. Immunol., September 1, 2006; 177(5): 3421 - 3426. [Abstract] [Full Text] [PDF] Y. Furumoto, S. Brooks, A. Olivera, Y. Takagi, M. Miyagishi, K. Taira, R. Casellas, M. A. Beaven, A. M. Gilfillan, and J. Rivera Cutting Edge: Lentiviral Short Hairpin RNA Silencing of PTEN in Human Mast Cells Reveals Constitutive Signals That Promote Cytokine Secretion and Cell Survival J. Immunol., May 1, 2006; 176(9): 5167 - 5171. [Abstract] [Full Text] [PDF] H. Qiao, M. V. Andrade, F. A. Lisboa, K. Morgan, and M. A. 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