HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miura, K. Articles by MacGlashan, D. W. Search for Related Content PubMed PubMed Citation Articles by Miura, K. Articles by MacGlashan, D. W., Jr.

Localizing a Control Region in the Pathway to Leukotriene C₄ Secretion Following Stimulation of Human Basophils with Anti-IgE Antibody¹

Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224

Mediator release from human basophils is a self-limited process, but down-regulation of the signaling cascades leading to secretion of leukotriene C₄ (LTC₄) is controlled independently of the pathway leading to IL-4 secretion. In the current studies, we have explored the regulation of upstream signaling events leading to activation of extracellular signal-related kinases (ERKs; previously shown to be required for LTC₄ generation) in human basophils. IgE-, but not FMLP-mediated activation, induced sustained tyrosine phosphorylation of syk, of shc, and an association of shc to the Grb2/son of sevenless 2 complex. In contrast, IgE-mediated activation resulted in transient activation of p21^ras and mitogen-activated protein/ERK kinase 1, which were kinetically associated with phosphorylation of ERKs. The canonical Shc/Grb2/son of sevenless pathway to activation of p21^ras is therefore sustained, while p21^ras activity is not. We have previously shown that phosphatidylinositol 3 kinase activity is required for p21^ras activity and, in the current studies, we show that of the p85-sensitive forms of p110 possible, basophils express only p110 and that there are no changes in association between p21^ras and p110 in stimulated basophils. We used the generation of phospho-Akt as a marker of the presence of phosphatidylinositol-3,4,5-trisphosphate and found that phospho-Akt is transient on a time scale consistent with p21^ras activity. On the basis of information obtained in these and other studies, we localize down-regulation of IgE-mediated LTC₄ secretion to a region of the signaling cascade antecedent to p21^ras activation, downstream of phosphatidylinositol 3 kinase activity and probably involving regulation of phosphatidylinositol-3,4,5-trisphosphate levels.

This article has been cited by other articles:

				B. M. Vonakis, D. W. MacGlashan Jr, N. Vilarino, J. M. Langdon, R. S. Scott, and S. M. MacDonald Distinct characteristics of signal transduction events by histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP)-induced priming and activation of human basophils Blood, February 15, 2008; 111(4): 1789 - 1796. [Abstract] [Full Text] [PDF]

				D. MacGlashan Jr. and N. Vilarino Nonspecific Desensitization, Functional Memory, and the Characteristics of SHIP Phosphorylation following IgE-Mediated Stimulation of Human Basophils J. Immunol., July 15, 2006; 177(2): 1040 - 1051. [Abstract] [Full Text] [PDF]

				N. Vilarino and D. W. MacGlashan Jr Actin cytoskeleton-dependent down-regulation of early IgE-mediated signaling in human basophils J. Leukoc. Biol., May 1, 2004; 75(5): 928 - 937. [Abstract] [Full Text] [PDF]

				D. MacGlashan Jr. Two Regions of Down-Regulation in the IgE-Mediated Signaling Pathway in Human Basophils J. Immunol., May 15, 2003; 170(10): 4914 - 4925. [Abstract] [Full Text] [PDF]

				A. de Paulis, G. Florio, N. Prevete, M. Triggiani, I. Fiorentino, A. Genovese, and G. Marone HIV-1 Envelope gp41 Peptides Promote Migration of Human Fc{epsilon}RI+ Cells and Inhibit IL-13 Synthesis Through Interaction with Formyl Peptide Receptors J. Immunol., October 15, 2002; 169(8): 4559 - 4567. [Abstract] [Full Text] [PDF]