Abstract
Detergent-resistant plasma membrane structures, such as caveolae, have been implicated in signalling, transport, and vesicle trafficking functions. Using sucrose gradient ultracentrifugation, we have isolated low-density, Triton X-100-insoluble membrane domains from RBL-2H3 mucosal mast cells that contain several markers common to caveolae, including a src-family tyrosine kinase, p53/56lyn. Aggregation of Fc epsilon RI, the high-affinity IgE receptor, causes a significant increase in the amount of p53/56lyn associated with these low-density membrane domains. Under our standard conditions for lysis, IgE-Fc epsilon RI fractionates with the majority of the solubilized proteins, whereas aggregated receptor complexes are found at a higher density in the gradient. Stimulated translocation of p53/56lyn is accompanied by increased tyrosine phosphorylation of several proteins in the low-density membrane domains as well as enhanced in vitro tyrosine kinase activity toward these proteins and an exogenous substrate. With a lower detergent-to-cell ratio during lysis, significant Fc epsilon RI remains associated with these membrane domains, consistent with the ability to coimmunoprecipitate tyrosine kinase activity with Fc epsilon RI under similar lysis conditions [Pribluda, V. S., Pribluda, C. & Metzger, H. (1994) Proc. Natl. Acad. Sci. USA 91, 11246-11250]. These results indicate that specialized membrane domains may be directly involved in the coupling of receptor aggregation to the activation of signaling events.
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- Anderson R. G. Caveolae: where incoming and outgoing messengers meet. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10909–10913. doi: 10.1073/pnas.90.23.10909. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barsumian E. L., Isersky C., Petrino M. G., Siraganian R. P. IgE-induced histamine release from rat basophilic leukemia cell lines: isolation of releasing and nonreleasing clones. Eur J Immunol. 1981 Apr;11(4):317–323. doi: 10.1002/eji.1830110410. [DOI] [PubMed] [Google Scholar]
- Basciano L. K., Berenstein E. H., Kmak L., Siraganian R. P. Monoclonal antibodies that inhibit IgE binding. J Biol Chem. 1986 Sep 5;261(25):11823–11831. [PubMed] [Google Scholar]
- Beaven M. A., Metzger H. Signal transduction by Fc receptors: the Fc epsilon RI case. Immunol Today. 1993 May;14(5):222–226. doi: 10.1016/0167-5699(93)90167-j. [DOI] [PubMed] [Google Scholar]
- Benhamou M., Siraganian R. P. Protein-tyrosine phosphorylation: an essential component of Fc epsilon RI signaling. Immunol Today. 1992 Jun;13(6):195–197. doi: 10.1016/0167-5699(92)90152-w. [DOI] [PubMed] [Google Scholar]
- Brown D. A., Rose J. K. Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell. 1992 Feb 7;68(3):533–544. doi: 10.1016/0092-8674(92)90189-j. [DOI] [PubMed] [Google Scholar]
- Brown D. The tyrosine kinase connection: how GPI-anchored proteins activate T cells. Curr Opin Immunol. 1993 Jun;5(3):349–354. doi: 10.1016/0952-7915(93)90052-t. [DOI] [PubMed] [Google Scholar]
- Chang W. J., Ying Y. S., Rothberg K. G., Hooper N. M., Turner A. J., Gambliel H. A., De Gunzburg J., Mumby S. M., Gilman A. G., Anderson R. G. Purification and characterization of smooth muscle cell caveolae. J Cell Biol. 1994 Jul;126(1):127–138. doi: 10.1083/jcb.126.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Creutz C. E. The annexins and exocytosis. Science. 1992 Nov 6;258(5084):924–931. doi: 10.1126/science.1439804. [DOI] [PubMed] [Google Scholar]
- Dráberová L., Dráber 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 Apr 15;90(8):3611–3615. doi: 10.1073/pnas.90.8.3611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eiseman E., Bolen J. B. Engagement of the high-affinity IgE receptor activates src protein-related tyrosine kinases. Nature. 1992 Jan 2;355(6355):78–80. doi: 10.1038/355078a0. [DOI] [PubMed] [Google Scholar]
- Fiedler K., Kobayashi T., Kurzchalia T. V., Simons K. Glycosphingolipid-enriched, detergent-insoluble complexes in protein sorting in epithelial cells. Biochemistry. 1993 Jun 29;32(25):6365–6373. doi: 10.1021/bi00076a009. [DOI] [PubMed] [Google Scholar]
- Fra A. M., Williamson E., Simons K., Parton R. G. Detergent-insoluble glycolipid microdomains in lymphocytes in the absence of caveolae. J Biol Chem. 1994 Dec 9;269(49):30745–30748. [PubMed] [Google Scholar]
- Fujimoto T. Calcium pump of the plasma membrane is localized in caveolae. J Cell Biol. 1993 Mar;120(5):1147–1157. doi: 10.1083/jcb.120.5.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fujimoto T., Nakade S., Miyawaki A., Mikoshiba K., Ogawa K. Localization of inositol 1,4,5-trisphosphate receptor-like protein in plasmalemmal caveolae. J Cell Biol. 1992 Dec;119(6):1507–1513. doi: 10.1083/jcb.119.6.1507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guo N. H., Her G. R., Reinhold V. N., Brennan M. J., Siraganian R. P., Ginsburg V. 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 Aug 5;264(22):13267–13272. [PubMed] [Google Scholar]
- Holowka D., Baird B. Recent evidence for common signalling mechanisms among immunoreceptors that recognize foreign antigens. Cell Signal. 1992 Jul;4(4):339–349. doi: 10.1016/0898-6568(92)90029-8. [DOI] [PubMed] [Google Scholar]
- Hutchcroft J. E., Geahlen R. L., Deanin G. G., Oliver J. M. Fc epsilon RI-mediated tyrosine phosphorylation and activation of the 72-kDa protein-tyrosine kinase, PTK72, in RBL-2H3 rat tumor mast cells. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9107–9111. doi: 10.1073/pnas.89.19.9107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jouvin M. H., Adamczewski M., Numerof R., Letourneur O., Vallé A., Kinet J. P. 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 Feb 25;269(8):5918–5925. [PubMed] [Google Scholar]
- Lipsich L. A., Lewis A. J., Brugge J. S. Isolation of monoclonal antibodies that recognize the transforming proteins of avian sarcoma viruses. J Virol. 1983 Nov;48(2):352–360. doi: 10.1128/jvi.48.2.352-360.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lisanti M. P., Scherer P. E., Tang Z., Sargiacomo M. Caveolae, caveolin and caveolin-rich membrane domains: a signalling hypothesis. Trends Cell Biol. 1994 Jul;4(7):231–235. doi: 10.1016/0962-8924(94)90114-7. [DOI] [PubMed] [Google Scholar]
- Lisanti M. P., Scherer P. E., Vidugiriene J., Tang Z., Hermanowski-Vosatka A., Tu Y. H., Cook R. F., Sargiacomo M. Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: implications for human disease. J Cell Biol. 1994 Jul;126(1):111–126. doi: 10.1083/jcb.126.1.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu F. T., Bohn J. W., Ferry E. L., Yamamoto H., Molinaro C. A., Sherman L. A., Klinman N. R., Katz D. H. Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization. J Immunol. 1980 Jun;124(6):2728–2737. [PubMed] [Google Scholar]
- McCloskey M. A. Cholera toxin potentiates IgE-coupled inositol phospholipid hydrolysis and mediator secretion by RBL-2H3 cells. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7260–7264. doi: 10.1073/pnas.85.19.7260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Minoguchi K., Benhamou M., Swaim W. D., Kawakami Y., Kawakami T., Siraganian R. P. Activation of protein tyrosine kinase p72syk by Fc epsilon RI aggregation in rat basophilic leukemia cells. p72syk is a minor component but the major protein tyrosine kinase of pp72. J Biol Chem. 1994 Jun 17;269(24):16902–16908. [PubMed] [Google Scholar]
- Minoguchi K., Swaim W. D., Berenstein E. H., Siraganian R. P. 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 Feb 18;269(7):5249–5254. [PubMed] [Google Scholar]
- Mumby S. M., Kleuss C., Gilman A. G. Receptor regulation of G-protein palmitoylation. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2800–2804. doi: 10.1073/pnas.91.7.2800. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Narasimhan V., Holowka D., Fewtrell C., Baird B. Cholera toxin increases the rate of antigen-stimulated calcium influx in rat basophilic leukemia cells. J Biol Chem. 1988 Dec 25;263(36):19626–19632. [PubMed] [Google Scholar]
- Paolini R., Jouvin M. H., Kinet J. P. Phosphorylation and dephosphorylation of the high-affinity receptor for immunoglobulin E immediately after receptor engagement and disengagement. Nature. 1991 Oct 31;353(6347):855–858. doi: 10.1038/353855a0. [DOI] [PubMed] [Google Scholar]
- Paul W. E., Seder R. A., Plaut M. Lymphokine and cytokine production by Fc epsilon RI+ cells. Adv Immunol. 1993;53:1–29. [PubMed] [Google Scholar]
- Pribluda V. S., Pribluda C., Metzger H. Transphosphorylation as the mechanism by which the high-affinity receptor for IgE is phosphorylated upon aggregation. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11246–11250. doi: 10.1073/pnas.91.23.11246. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Resh M. D. Myristylation and palmitylation of Src family members: the fats of the matter. Cell. 1994 Feb 11;76(3):411–413. doi: 10.1016/0092-8674(94)90104-x. [DOI] [PubMed] [Google Scholar]
- Sargiacomo M., Sudol M., Tang Z., Lisanti M. P. Signal transducing molecules and glycosyl-phosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells. J Cell Biol. 1993 Aug;122(4):789–807. doi: 10.1083/jcb.122.4.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schnitzer J. E., Oh P., Jacobson B. S., Dvorak A. M. Caveolae from luminal plasmalemma of rat lung endothelium: microdomains enriched in caveolin, Ca(2+)-ATPase, and inositol trisphosphate receptor. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1759–1763. doi: 10.1073/pnas.92.5.1759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shenoy-Scaria A. M., Dietzen D. J., Kwong J., Link D. C., Lublin D. M. Cysteine3 of Src family protein tyrosine kinase determines palmitoylation and localization in caveolae. J Cell Biol. 1994 Jul;126(2):353–363. doi: 10.1083/jcb.126.2.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas J. L., Holowka D., Baird B., Webb W. W. Large-scale co-aggregation of fluorescent lipid probes with cell surface proteins. J Cell Biol. 1994 May;125(4):795–802. doi: 10.1083/jcb.125.4.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Veillette A., Bookman M. A., Horak E. M., Bolen J. B. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell. 1988 Oct 21;55(2):301–308. doi: 10.1016/0092-8674(88)90053-0. [DOI] [PubMed] [Google Scholar]
- Weiss A., Littman D. R. Signal transduction by lymphocyte antigen receptors. Cell. 1994 Jan 28;76(2):263–274. doi: 10.1016/0092-8674(94)90334-4. [DOI] [PubMed] [Google Scholar]
- WoldeMussie E., Maeyama K., Beaven M. A. Loss of secretory response of rat basophilic leukemia (2H3) cells at 40 degrees C is associated with reversible suppression of inositol phospholipid breakdown and calcium signals. J Immunol. 1986 Sep 1;137(5):1674–1680. [PubMed] [Google Scholar]
- 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 U S A. 1994 Nov 8;91(23):11251–11255. doi: 10.1073/pnas.91.23.11251. [DOI] [PMC free article] [PubMed] [Google Scholar]