FcεRI Signaling in Specialized Membrane Domains

  • Kenneth A. Field
  • David Holowka
  • Barbara Baird
Chapter

Abstract

Aggregation of FcεRI, the receptor with high affinity for IgE found on mast cells and basophils, initiates a signaling cascade culminating in the secretion of granules containing inflammatory mediators from these cells, as well as the production of other inflammatory agents. The earliest detectable events following receptor aggregation involve the tyrosine phosphorylation of FcεRI within immunoreceptor tyrosine-based activation motifs (ITAMs). This initial phosphorylation step, referred to here as receptor activation, is mediated by the protein tyrosine kinase (PTK) Lyn, and it is regulated by unidentified tyrosine phosphatases. The phosphorylated ITAMs recruit SH-2 domain-containing signaling proteins, including Syk, a ZAP-70-related PTK that binds the phosphorylated receptor γ-chains.

Keywords

Mast Cell Protein Tyrosine Kinase Membrane Domain Plasma Membrane Domain Brane Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Zhang J, Berenstein EH, Evans RL, et al. Trans-fection of Syk protein tyrosine kinase reconstitutes high affinity IgE receptor-mediated degranulation in a Syk-negative variant of rat basophilic leukemia RBL-2H3 cells. J Exp Med 1996;184:71–79.PubMedCrossRefGoogle Scholar
  2. 2.
    Scharenberg AM, Lin S, Cuenod B, et al. Reconstitution of interactions between tyrosine kinases and the high affinity IgE receptor which are controlled by receptor clustering. EMBO J 1995;14:3385–3394.PubMedGoogle Scholar
  3. 3.
    Adamczewski M, Numerof RP, Koretzky GA, et al. Regulation by CD45 of the tyrosine phosphorylation of high affinity IgE receptor beta- and gamma-chains. J Immunol 1995;154:3047–3055.PubMedGoogle Scholar
  4. 4.
    Resh MD. Myristylation and palmitylation of Src family members: the fats of the matter. Cell 1994;76:411–413.PubMedCrossRefGoogle Scholar
  5. 5.
    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.PubMedCrossRefGoogle Scholar
  6. 6.
    Eiseman E, Bolen JB. Engagement of the high-affinity IgE receptor activates src protein-related tyrosine kinases. Nature (Lond) 1992;355:78–80.PubMedCrossRefGoogle Scholar
  7. 7.
    Jouvin MH, Adamczewski M, Numerof R, et al. Differential control of the tyrosine kinases Lyn and Syk by the two signaling chains of the high affinity immunoglobulin E receptor. J Biol Chem 1994;269:5918–5925.Google Scholar
  8. 8.
    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.PubMedCrossRefGoogle Scholar
  9. 9.
    Mao SY, Yamashita T, Metzger H. Chemical cross-linking of IgE-receptor complexes in RBL-2H3 cells. Biochemistry 1995;34:1968–1977.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 11.
    Alber G, Miller L, Jelsema CL, et al. Structure-function relationships in the mast cell high affinity receptor for IgE. Role of the cytoplasmic domains and of the beta subunit. J Biol Chem 1991;266:22613–22620.PubMedGoogle Scholar
  12. 12.
    Lin S, Cicala C, Scharenberg AM, et al. The FcεRIβ subunit functions as an amplifier of FcεRIγ-mediated cell activation signals. Cell 1996;85:985–995.PubMedCrossRefGoogle Scholar
  13. 13.
    Juergens M, Wollenberg A, Hanau D, et al. Activation of human epidermal langerhans cells by engagement of the high affinity receptor for IgE, Fc-epsilon-RI. J Immunol 1995;155:5184–5189.Google Scholar
  14. 14.
    Eiseman E, Bolen JB. Signal transduction by the cytoplasmic domains of Fc-epsilon-RI-gamma and TCR-zeta in rat basophilic leukemia cells. J Biol Chem 1992;267:21027–21032.PubMedGoogle Scholar
  15. 15.
    Wilson BS, Kapp N, Lee RJ, et al. Distinct functions of the Fc-epsilon-R1 gamma and beta sub-units in the control of Fc-epsilon-RI-mediated tyrosine kinase activation and signaling responses in RBL-2H3 mast cells. J Biol Chem 1995;270:4013–4022.PubMedCrossRefGoogle Scholar
  16. 16.
    Repetto B, Bandara G, Kado-Fong H, et al. Functional contributions of the FcεRIα and FcεRIγ subunit domains in FcεRI-mediated signaling in mast cells. J Immunol 1996;156:4876–4883.PubMedGoogle Scholar
  17. 17.
    Brown DA, Rose JK. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell 1992;68:533–544.PubMedCrossRefGoogle Scholar
  18. 18.
    Yamada E. The fine structure of the gall bladder epithelium of the mouse. J Biophys Biochem Cytol 1955;1:445–458.PubMedCrossRefGoogle Scholar
  19. 19.
    Rothberg KG, Heuser JE, Donzell WC, et al. Caveolin, a protein component of caveolae membrane coats. Cell 1992;68:673–682.PubMedCrossRefGoogle Scholar
  20. 20.
    Lisanti MP, Tang ZL, Sargiacomo M. Caveolin forms a hetero-oligomeric protein complex that interacts with an apical GPI-linked protein: implications for the biogenesis of caveolae. J Cell Biol 1993;123:595–604.PubMedCrossRefGoogle Scholar
  21. 21.
    Fra AM, Williamson E, Simons K, et al. Detergent-insoluble glycolipid microdomains in lymphocytes in the absence of caveolae. J Biol Chem 1994;269:30745–30748.PubMedGoogle Scholar
  22. 22.
    Parolini I, Sargiacomo M, Lisanti MP, et al. Signal transduction and glycophosphatidylinositol-linked proteins (lyn, lck, CD4, CD45, G proteins, and CD55) selectively localize in Triton-insoluble plasma membrane domains of human leukemic cell lines and normal granulocytes. Blood 1996;87:3783–3794.PubMedGoogle Scholar
  23. 23.
    Fra AM, Williamson E, Simons K, et al. De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin. Proc Natl Acad Sci USA 1995;92:8655–8659.PubMedCrossRefGoogle Scholar
  24. 24.
    Schroeder R, London E, Brown D. Interactions between saturated acyl chains confer detergent resistance on lipids and glycosylphosphatidylinositol (GPI)-anchored proteins: GPI-anchored proteins in liposomes and cells show similar behavior. Proc Natl Acad Sci USA 1994;91:12130–12134.PubMedCrossRefGoogle Scholar
  25. 25.
    Shenoy-Scaria AM, Dietzen DJ, Kwong J, et al. Cysteine 3 of Src family protein tyrosine kinase determines palmitoylation and localization in caveolae. J Cell Biol 1994;126:353–363.PubMedCrossRefGoogle Scholar
  26. 26.
    Arreaza G, Melkonian KA, Lafevre-Bernt M, et al. Triton X-100-resistant membrane complexes from cultured kidney epithelial cells contain the src family protein tyrosine kinase p62-yes. J Biol Chem 1994;269:19123–19127.PubMedGoogle Scholar
  27. 27.
    Sargiacomo M, Sudol M, Tang Z, et al. Signal transducing molecules and glycosylphosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells. J Cell Biol 1993;122:789–807.PubMedCrossRefGoogle Scholar
  28. 28.
    Mayor S, Rothberg KG, Maxfield FR. Sequestration of GPI-anchored proteins in caveolae triggered by cross-linking. Science 1994;264:1948–1951.PubMedCrossRefGoogle Scholar
  29. 29.
    Schnitzer JE, Mcintosh DP, Dvorak AM, et al. Separation of caveolae from associated microdomains of GPI-anchored proteins. Science 1995;269:1435–1439.PubMedCrossRefGoogle Scholar
  30. 30.
    Shenoy-Scaria AM, Gauen LK, Kwong J, et al. Palmitylation of an amino-terminal cysteine motif of protein tyrosine kinases p56lck and p59fyn mediates interaction with glycosylphosphatidylinositol-anchored proteins. Mol Cell Biol 1993;13:6385–6392.PubMedGoogle Scholar
  31. 31.
    Brown D. The tyrosine kinase connection: how GPI-anchored proteins activate T cells. Curr Opin Immunol 1993;5:349–354.PubMedCrossRefGoogle Scholar
  32. 32.
    van’t Hof W, Resh MD. Rapid plasma membrane anchoring of newly synthesized p59fyn: selective requirement for NH2-terminal myristoylation and palmitoylation at cysteine-3. J Cell Biol 1997;136:1023–1035.PubMedCrossRefGoogle Scholar
  33. 33.
    Lisanti MP, Scherer PE, Tang Z, et al. Caveolae, caveolin and caveolin-rich membrane domains: a signalling hypothesis. Trends Cell Biol 1994;4:231–235.PubMedCrossRefGoogle Scholar
  34. 34.
    Chang WJ, Ying YS, Rothberg KG, et al. Purification and characterization of smooth muscle cell caveolae. J Cell Biol 1994;126:127–138.PubMedCrossRefGoogle Scholar
  35. 35.
    Lisanti MP, Scherer PE, Vidugiriene J, et al. Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: implications for human disease. J Cell Biol 1994;126:111–126.PubMedCrossRefGoogle Scholar
  36. 36.
    Liu P, Anderson RGW. Compartmentalized production of ceramide at the cell surface. J Biol Chem 1995;270:27179–27185.PubMedCrossRefGoogle Scholar
  37. 37.
    Liu P, Ying Y, Ko YG, et al. Localization of platelet-derived growth factor-stimulated phosphorylation cascade to caveolae. J Biol Chem 1996;271:10299–10303.PubMedCrossRefGoogle Scholar
  38. 38.
    Mineo C, James GL, Smart EJ, et al. Localization of epidermal growth factor-stimulated ras/raf-1 interaction to caveolae membrane. J Biol Chem 1996;271:11930–11935.PubMedCrossRefGoogle Scholar
  39. 39.
    Liu J, Oh P, Horner T, et al. Organized endothelial cell surface signal transduction in caveolae distinct from glycosylphosphatidylinositol-anchored protein microdomains. J Biol Chem 1997;272:7211–7222.PubMedCrossRefGoogle Scholar
  40. 40.
    Field KA, Holowka D, Baird B. FcεRI-mediated recruitment of p53/56lyn to detergent resistant membrane domains accompanies cellular signaling. Proc Natl Acad Sci USA 1995;92:9201–9205.PubMedCrossRefGoogle Scholar
  41. 41.
    Gorodinsky A, Harris DA. Glycolipid-anchored proteins in neuroblastoma cells form detergent-resistant complexes without caveolin. J Cell Biol 1995;129:619–627.PubMedCrossRefGoogle Scholar
  42. 42.
    Draberova L, Draber P. Thy-1 glycoprotein and src-like protein-tyrosine kinase p53/p56lyn are associated in large detergent-resistant complexes in rat basophilic leukemia cells. Proc Natl Acad Sci U S A 1993;90:3611–3615.PubMedCrossRefGoogle Scholar
  43. 43.
    Draberova L, Amoui M, Draber P. Thy-1-mediated activation of rat mast cells: the role of thy-1 membrane microdomains. Immunology 1996;87:141–148.PubMedGoogle Scholar
  44. 44.
    Stefanova I, Horejsi V, Ansotegui IJ, et al. GPI-anchored cell-surface molecules complexed to protein tyrosine kinases. Science 1991;254:1016–1019.PubMedCrossRefGoogle Scholar
  45. 45.
    Cinek T, Horejsi V. The nature of large noncovalent complexes containing glycosylphosphatidylinositol-anchored membrane glycoproteins and protein tyrosine kinases. J Immunol 1992;149:2262–2270.PubMedGoogle Scholar
  46. 46.
    Shenoy-Scaria AM, Kwong J, Fujita T, et al. Signal transduction through decay-accelerating factor. Interaction of glycosylphosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn. J Immunol 1992;149:3535–3541.PubMedGoogle Scholar
  47. 47.
    Minoguchi K, Swaim WD, Berenstein EH, et al. Src family tyrosine kinase p53/56lyn, a serine kinase and Fc epsilon RI associate with alpha-galactosyl derivatives of ganglioside GD1b in rat basophilic leukemia RBL-2H3 cells. J Biol Chem 1994;269:5249–5254.PubMedGoogle Scholar
  48. 48.
    Wofsy C, Kent UM, Mao SY, et al. Kinetics of tyrosine phosphorylation when IgE dimers bind to Fc-epsilon receptors on rat basophilic leukemia cells. J Biol Chem 1995;270:20264–20272.PubMedCrossRefGoogle Scholar
  49. 49.
    Paolini R, Numerof R, Kinet JP. Phosphorylation-dephosphorylation of high-affinity IgE receptors: a mechanism for coupling-uncoupling a large signaling complex. Proc Natl Acad Sci USA 1992;89:10733–10737.PubMedCrossRefGoogle Scholar
  50. 50.
    Chan AC, Desai DM, Weiss A. The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction. Annu Rev Immunol 1994;12:555–592.PubMedCrossRefGoogle Scholar
  51. 51.
    Basciano LK, Berenstein EH, Kmak L, et al. Monoclonal antibodies that inhibit IgE binding. J Biol Chem 1986;261:11823–11831.PubMedGoogle Scholar
  52. 52.
    Thomas JL, Holowka D, Baird B, et al. Large-scale co-aggregation of fluorescent lipid probes with cell surface proteins. J Cell Biol 1994;125:795–802.PubMedCrossRefGoogle Scholar
  53. 53.
    Beaven MA, Baumgartner RA. Downstream signals initiated in mast cells by FcεRI and other receptors. Curr Opin Immunol 1996;8:766–772.PubMedCrossRefGoogle Scholar
  54. 54.
    Holowka D, Hine C, Baird B. Alterations in cellular lipid composition affect the interactions of aggregated Fc-epsilon-RI with p53–56-lyn and the microfilament cytoskeleton. FASEB J 1996;10:A1214.Google Scholar
  55. 55.
    Pierini L, Harris NT, Holowka D, et al. Evidence supporting a role for microfilaments in regulating the coupling between poorly-dissociable IgE-FcεRI aggregates and downstream signaling pathways. Biochemistry 1997;36:7447–7456.PubMedCrossRefGoogle Scholar
  56. 56.
    Schuh SM, Lublin DM. The Triton-insoluble fraction of p56-lck has increased protein tyrosine kinase activity. FASEB J 1995;9:A1302.Google Scholar
  57. 57.
    Yan SR, Fumagalli L, Berton G. Activation of src family kinases in human neutrophils. Evidence that p58c-fgr and p53/56lyn redistributed to a Triton X-100-insoluble cytoskeletal fraction, also enriched in the caveolar protein caveolin, display an enhanced kinase activity. FEBS Lett 1996;380:198–203.PubMedCrossRefGoogle Scholar
  58. 58.
    Rodgers W, Rose JK. Exclusion of CD45 inhibits activity of p56-lck associated with glycolipid-enriched membrane domains. J Cell Biol 1996;135:1515–1523.PubMedCrossRefGoogle Scholar
  59. 59.
    Benhamou M, Ryba NJ, Kihara H, et al. Protein-tyrosine kinase p72syk in high affinity IgE receptor signaling. Identification as a component of pp72 and association with the receptor gamma chain after receptor aggregation. J Biol Chem 1993;268:23318–23324.PubMedGoogle Scholar
  60. 60.
    Pierini L, Holowka D, Baird B. Fc-epsilon-RI-mediated association of 6-µm beads with RBL-2H3 mast cells results in exclusion of signaling proteins from the forming phagosome and abrogation of normal downstream signaling. J Cell Biol 1996;134:1427–1439.PubMedCrossRefGoogle Scholar
  61. 61.
    Chang EY, Zheng Y, Holowka D, et al. Alteration of lipid composition modulates Fc-epsilon-RI signaling in RBL-2H3 cells. Biochemistry 1995;34:4376–4384.PubMedCrossRefGoogle Scholar
  62. 62.
    Kinet JP, Alcaraz G, Leonard A, et al. Dissociation of the receptor for immunoglobulin E in mild detergents. Biochemistry 1985;24:4117–4124.PubMedCrossRefGoogle Scholar
  63. 63.
    Minami Y, Taniguchi T. IL-2 signaling: recruitment and activation of multiple protein tyrosine kinases by the components of the IL-2 receptor. Curr Opin Cell Biol 1995;7:156–162.PubMedCrossRefGoogle Scholar
  64. 64.
    Guo NH, Her GR, Reinhold VN, et al. Monoclonal antibody AA4, which inhibits binding of IgE to high affinity receptors on rat basophilic leukemia cells, binds to novel alpha-galactosyl derivatives of ganglioside GD1b. J Biol Chem 1989;264:13267–13272.PubMedGoogle Scholar
  65. 65.
    Kinet JP, Quarto R, Perez MR, et al. Non-covalently and covalently bound lipid on the receptor for immunoglobulin E. Biochemistry 1985;24:7342–7348.PubMedCrossRefGoogle Scholar
  66. 66.
    Singer SJ, Nicolson GL. The fluid mosaic model of the structure of cell membranes. Science 1972;175:720–731.PubMedCrossRefGoogle Scholar
  67. 67.
    Edidin M, Kuo SC, Sheetz MP. Lateral movements of membrane glycoproteins restricted by dynamic cytoplasmic barriers. Science 1991;254:1379–1382.PubMedCrossRefGoogle Scholar
  68. 68.
    Holowka D, Baird B. Antigen-mediated IgE receptor aggregation and signaling: a window on cell surface structure and dynamics. Annu Rev Biophys Biomol Struct 1996;25:79–112.PubMedCrossRefGoogle Scholar
  69. 69.
    Schlessinger J, Webb WW, Elson EL, et al. Lateral motion and valence of Fc receptors on rat peritoneal mast cells. Nature (Lond) 1976;264:550–552.PubMedCrossRefGoogle Scholar
  70. 70.
    Mao SY, Varin BN, Edidin M, et al. Immobilization and internalization of mutated IgE receptors in transfected cells. J Immunol 1991;146:958–966.PubMedGoogle Scholar
  71. 71.
    Myers JN, Holowka D, Baird B. Rotational motion of monomeric and dimeric immunoglobulin E-receptor complexes. Biochemistry 1992;31:567–575.PubMedCrossRefGoogle Scholar
  72. 72.
    Pecht I, Ortega E, Jovin TM. Rotational dynamics of the Fc-epsilon receptor on mast cells monitored by specific monoclonal antibodies and IgE. Biochemistry 1991;30:3450–3458.PubMedCrossRefGoogle Scholar
  73. 73.
    Zidovetzki R, Bartholdi M, Arndt JD, et al. Rotational dynamics of the Fc receptor for immunoglobulin E on histamine-releasing rat basophilic leukemia cells. Biochemistry 1986;25:4397–4401.PubMedCrossRefGoogle Scholar
  74. 74.
    Chang EY, Mao SY, Metzger H, et al. Effects of subunit mutation on the rotational dynamics of Fc-epsilon-RI, the high affinity receptor for IgE, in transfected cells. Biochemistry 1995;34:6093–6099.PubMedCrossRefGoogle Scholar
  75. 75.
    Menon AK, Holowka D, Webb WW, et al. Clustering mobility and triggering activity of small oligomers of immunoglobulin E on rat basophilic leukemia cells. J Cell Biol 1986;102:534–540.PubMedCrossRefGoogle Scholar
  76. 76.
    Menon AK, Holowka D, Webb WW, et al. Cross-linking of receptor-bound immunoglobulin E to aggregates larger than dimers leads to rapid immobilization. J Cell Biol 1986;102:541–550.PubMedCrossRefGoogle Scholar
  77. 77.
    Apgar JR. Antigen-induced cross-linking of the IgE receptor leads to an association with the detergent-insoluble membrane skeleton of rat basophilic leukemia RBL-2H3 cells. J Immunol 1990;145:3814–3822.PubMedGoogle Scholar
  78. 78.
    Apgar JR. Association of the cross-linked IgE receptor with the membrane skeleton is independent of the known signaling mechanisms in rat basophilic leukemia cells. Cell Regul 1991;2:181–192.PubMedGoogle Scholar
  79. 79.
    Robertson D, Holowka D, Baird B. Cross-linking of immunoglobulin E-receptor complexes induces their interaction with the cytoskeleton of rat basophilic leukemia cells. J Immunol 1986;136:4565–4572.PubMedGoogle Scholar
  80. 80.
    Seagrave J, Oliver JM. Antigen-dependent transition of IgE to a detergent-insoluble form is associated with reduced IgE receptor-dependent secretion from RBL-2H3 mast cells. J Cell Physiol 1990;144:128–136.PubMedCrossRefGoogle Scholar
  81. 81.
    Zhang F, Crise B;, Su B, et al. Lateral diffusion of membrane-spanning and glyco-sylphosphatidylinositol-linked proteins: toward establishing rules governing the lateral mobility of membrane proteins. J Cell Biol 1991;115:75–84.PubMedCrossRefGoogle Scholar
  82. 82.
    Hannan LA, Lisanti MP, Rodriguez-Boulan E, et al. Correctly sorted molecules of a GPI-anchored protein are clustered and immobile when they arrive at the apical surface of MDCK cells. J Cell Biol 1993;120:353–358.PubMedCrossRefGoogle Scholar
  83. 83.
    Rock P, Allietta M, Young WWJ, et al. Organization of glycosphingolipids in phosphatidylcholine bilayers: use of antibody molecules and Fab fragments as morphologic markers. Biochemistry 1990;29:8484–8490.PubMedCrossRefGoogle Scholar
  84. 84.
    Sheets ED, Lee GM, Simson R, et al. Transient confinement of a glycosylphosphatidylinositol-anchored protein in the plasma membrane. Biochemistry 1997;36:12449–12458.PubMedCrossRefGoogle Scholar
  85. 85.
    Schnitzer JE, Oh P, Jacobson BS, et al. Caveolae from luminal plasmalemma of rat lung endothelium: microdomains enriched in caveolin, Ca2+-ATPase, and inositol trisphosphate receptor. Proc Natl Acad Sci USA 1995;92:1759–1763.PubMedCrossRefGoogle Scholar
  86. 86.
    Schnitzer JE, Liu J, Oh P. Endothelial caveolae have the molecular transport machinery for vesicle budding, docking, and fusion including VAMP, NSF, SNAP, annexins, and GTPases. J Biol Chem 1995;270:14399–14404.PubMedCrossRefGoogle Scholar
  87. 87.
    Lawson D, Fewtrell C, Raff MC. Localized mast cell degranulation induced by concanavalin A-sepharose beads. J Cell Biol 1978;79:394–400.PubMedCrossRefGoogle Scholar
  88. 88.
    Field KA, Holowka D, Baird B. Structural aspects of the association of FcεRI with detergent resistant membranes. J Biol Chem 1999, in press.Google Scholar

Copyright information

© Springer-Verlag New York, Inc. 1999

Authors and Affiliations

  • Kenneth A. Field
  • David Holowka
  • Barbara Baird

There are no affiliations available

Personalised recommendations