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Mast Cells

A Perspective: Regulation of IgE Receptor-Mediated Mast Cell Responses by a LAT-Organized Plasma Membrane-Localized Signaling Complex

Rivera J. · Arudchandran R. · Gonzalez-Espinosa C. · Manetz T.S. · Xirasagar S.

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Section on Chemical Immunology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Md., USA

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Int Arch Allergy Immunol 2001;124:137–141

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Article / Publication Details

First-Page Preview
Abstract of Mast Cells

Published online: January 24, 2012
Issue release date: January – March

Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: https://www.karger.com/IAA

Abstract

Background: To understand how the high-affinity IgE receptor (FcΕRI) communicates with downstream effectors, we focused on exploring the functional importance of the FcΕRI-mediated formation and localization of a signaling complex that contains the hematopoietic cell-specific scaffolding protein linker for activation of T cells (LAT) and the guanine nucleotide exchange factor Vav1. Methods: Using the mast cell line RBL-2H3, we explored the localization of these proteins by confocal microscopy and cell fractionation. Additionally, the mechanism of function and the importance of LAT and Vav1 to mast cells was studied in genetically disrupted mice and in mast cells derived from their bone marrow. Results: We found that LAT, Vav1 and the adapter molecule SLP-76 associated in detergent-resistant microdomains (lipid rafts) found in the plasma membrane upon FcΕRI stimulation. In the absence of LAT, mast cells showed a remarkable loss of the secretory response and reduced cytokine responses. Vav1 deficiency also affected secretion, although not to the extent of LAT deficiency, and inhibited IL-2 and IFN-γ production. LAT- and Vav1-deficient mice showed reduced blood histamine levels after a systemic anaphylaxis challenge as compared to their normal counterparts. Conclusions: The results demonstrate that LAT is a central mediator in IgE receptor signaling by regulating multiple signaling pathways that affect mast cell degranulation and cytokine production. Vav1, a component of this LAT-containing signaling complex, regulates a specific subset of these responses.

© 2001 S. Karger AG, Basel


References

  1. McKeithan TW: Kinetic proofreading in T-cell receptor signal transduction. Proc Natl Acad Sci USA 1995;92:5042–5046.
    External Resources
  2. Racioppi L, Ronchese F, Matis LA, Germain RN: Peptide-major histocompatibility complex class II complexes with mixed agonist/antagonist properties provide evidence for ligand-related differences in T cell receptor-dependent intracellular signaling. J Exp Med 1993;177:1047–1060.
  3. Torigoe C, Inman JK, Metzger H: An unusual mechanism for ligand antagonism. Science 1998;281:568–572.
  4. Cantrell D: The real LAT steps forward. Trends Cell Biol 1998;8:180–182.
    External Resources
  5. Rudd CE: Adaptors and molecular scaffolds in immune cell signaling. Cell 1999;96:5–8.
  6. Pribluda VS, Pribluda C, Metzger H: Transphosphorylation as the mechanism by which the high-affinity receptor for IgE is phosphorylated upon aggregation. Proc Natl Acad Sci USA 1994;91:11246–11250.
  7. Wofsy C, Vonakis BM, Metzger H, Goldstein B: One Lyn molecule is sufficient to initiate phosphorylation of aggregated high-affinity IgE receptors. Proc Natl Acad Sci USA 1999;96:8615–8620.
  8. Eiseman E, Bolen JB: Engagement of the high-affinity IgE receptor activates src protein-related tyrosine kinases. Nature 1992;355:78–80.
  9. Yamashita T, Mao S-Y, Metzger H: Aggregation of the high-affinity IgE receptor and enhanced activity of p53/56lyn protein-tyrosine kinase. Proc Natl Acad Sci USA 1994;91:11251–11255.
    External Resources
  10. Field KA, Holowka D, Baird B: Compartmentalized activation of the high affinity immunoglobulin E receptor within membrane domains. J Biol Chem 1997;272:4276–4280.
  11. Baird B, Sheets ED, Holowka D: How does the plasma membrane participate in cellular signaling by receptors for immunoglobulin E? Biophys Chem 1999;82:109–119.
    External Resources
  12. Viola A, Schroeder S, Sakakibara Y, Lanzavecchia A: T lymphocyte costimulation mediated by reorganization of membrane microdomains. Science 1999;283:680–682.
  13. Saitoh S, Arudchandran R, Manetz TS, Zhang W, Sommers CL, Love PE, Rivera J, Samelson LE: LAT is essential for Fc(epsilon)RI-mediated mast cell activation. Immunity 2000;12:525–535.
  14. Goldschmidt-Clermont PJ, Kim JW, Machesky LM, Rhee SG, Pollard TD: Regulation of phospholipase C-gamma1 by profilin and tyrosine phosphorylation. Science 1991;251:1231–1233.
    External Resources
  15. Rhee SG, Choi KD: Regulation of inositol phospholipid-specific phospholipase C isozymes. J Biol Chem 1992;267:12393–12396.
    External Resources
  16. Yablonski D, Kuhne MR, Kadlecek T, Weiss A: Uncoupling of nonreceptor tyrosine kinases from PLC-γ1 in a SLP-76-deficient T cell. Science 1998;281:413–416.
  17. Van Leeuwen JEM, Samelson LE: T cell antigen-receptor signal transduction. Curr Opin Immunol 1999;11:242–248.
  18. Crabtree GR: Generic signals and specific outcomes: Signaling through Ca2+, calcineurin, and NF-AT. Cell 1999;96:611–614.
    External Resources
  19. Margolis B, Hu P, Katsav S, Li W, Oliver JM, Ullrich A, Weiss A, Schlessinger J: Tyrosine phosphorylation of Vav proto-oncogene product containing SH2 domain and transcription factor motifs. Nature 1992;356:71–74.
  20. Song JS, Gomez J, Stancato LF, Rivera J: Association of a p95 Vav-containing signaling complex with the FcεRI γ chain in the RBL-2H3 mast cell line. Evidence for a constitutive in vivo association of Vav with Grb2, Raf-1, and ERK2 in an active complex. J Biol Chem 1996;271:26962–26970.
  21. Arudchandran R, Brown MJ, Peirce MJ, Song JS, Zhang J, Siraganian RP, Blank U, Rivera J: The Src homology 2 domain of Vav is required for its compartmentation to the plasma membrane and activation of c-Jun NH(2)-terminal kinase 1. J Exp Med 2000;191:47–60.
  22. Zhang W, Trible RP, Samelson LE: LAT palmitoylation: Its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation. Immunity 1998;9:239–246.

Article / Publication Details

First-Page Preview
Abstract of Mast Cells

Published online: January 24, 2012
Issue release date: January – March

Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: https://www.karger.com/IAA


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