Abstract
Engagement of high-affinity IgE receptors leads to activation of tyrosine and serine/threonine kinases and the immediate phosphorylation of receptor beta (serine and tyrosine) and gamma (threonine and tyrosine) chains. Receptor disengagement leads to dephosphorylation of beta and gamma chains via the action of undefined phosphatases. Here we have identified five distinct polypeptides associated with the high-affinity IgE-receptor tetrameric complex, which apparently become phosphorylated and dephosphorylated in sequence with the beta and gamma chains. Like beta chain, polypeptides pp180, pp48, pp42, and pp28 are phosphorylated on serine and tyrosine, whereas pp125 is only phosphorylated on serine. The phosphorylation of each of these receptor-associated polypeptides is antigen-dose dependent and is restricted to activated receptor complexes. Furthermore the physical association between pp125 and the receptor is quantitatively affected by receptor phosphorylation and dephosphorylation, indicating a coupling-uncoupling mechanism. Finally, in vitro kinase experiments show that activated receptor complexes are also physically associated with tyrosine and serine/threonine kinases as part of a larger complex containing the phosphorylated polypeptides.
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- Alber G., Miller L., Jelsema C. L., Varin-Blank N., Metzger H. 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 Nov 25;266(33):22613–22620. [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]
- Benhamou M., Gutkind J. S., Robbins K. C., Siraganian R. P. Tyrosine phosphorylation coupled to IgE receptor-mediated signal transduction and histamine release. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5327–5330. doi: 10.1073/pnas.87.14.5327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benhamou M., Stephan V., Robbins K. C., Siraganian R. P. High-affinity IgE receptor-mediated stimulation of rat basophilic leukemia (RBL-2H3) cells induces early and late protein-tyrosine phosphorylations. J Biol Chem. 1992 Apr 15;267(11):7310–7314. [PubMed] [Google Scholar]
- Bieber T., de la Salle H., Wollenberg A., Hakimi J., Chizzonite R., Ring J., Hanau D., de la Salle C. Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI). J Exp Med. 1992 May 1;175(5):1285–1290. doi: 10.1084/jem.175.5.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burkhardt A. L., Brunswick M., Bolen J. B., Mond J. J. Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7410–7414. doi: 10.1073/pnas.88.16.7410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chan A. C., Irving B. A., Fraser J. D., Weiss A. The zeta chain is associated with a tyrosine kinase and upon T-cell antigen receptor stimulation associates with ZAP-70, a 70-kDa tyrosine phosphoprotein. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9166–9170. doi: 10.1073/pnas.88.20.9166. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Connelly P. A., Farrell C. A., Merenda J. M., Conklyn M. J., Showell H. J. Tyrosine phosphorylation is an early signaling event common to Fc receptor crosslinking in human neutrophils and rat basophilic leukemia cells (RBL-2H3). Biochem Biophys Res Commun. 1991 May 31;177(1):192–201. doi: 10.1016/0006-291x(91)91967-h. [DOI] [PubMed] [Google Scholar]
- Cooper J. A., Sefton B. M., Hunter T. Detection and quantification of phosphotyrosine in proteins. Methods Enzymol. 1983;99:387–402. doi: 10.1016/0076-6879(83)99075-4. [DOI] [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]
- Eiseman E., Bolen J. B. src-related tyrosine protein kinases as signaling components in hematopoietic cells. Cancer Cells. 1990 Oct;2(10):303–310. [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]
- Hutchcroft J. E., Harrison M. L., Geahlen R. L. Association of the 72-kDa protein-tyrosine kinase PTK72 with the B cell antigen receptor. J Biol Chem. 1992 Apr 25;267(12):8613–8619. [PubMed] [Google Scholar]
- Hutchcroft J. E., Harrison M. L., Geahlen R. L. B lymphocyte activation is accompanied by phosphorylation of a 72-kDa protein-tyrosine kinase. J Biol Chem. 1991 Aug 15;266(23):14846–14849. [PubMed] [Google Scholar]
- June C. H., Fletcher M. C., Ledbetter J. A., Samelson L. E. Increases in tyrosine phosphorylation are detectable before phospholipase C activation after T cell receptor stimulation. J Immunol. 1990 Mar 1;144(5):1591–1599. [PubMed] [Google Scholar]
- Justement L. B., Campbell K. S., Chien N. C., Cambier J. C. Regulation of B cell antigen receptor signal transduction and phosphorylation by CD45. Science. 1991 Jun 28;252(5014):1839–1842. doi: 10.1126/science.1648262. [DOI] [PubMed] [Google Scholar]
- Kim H. K., Kim J. W., Zilberstein A., Margolis B., Kim J. G., Schlessinger J., Rhee S. G. PDGF stimulation of inositol phospholipid hydrolysis requires PLC-gamma 1 phosphorylation on tyrosine residues 783 and 1254. Cell. 1991 May 3;65(3):435–441. doi: 10.1016/0092-8674(91)90461-7. [DOI] [PubMed] [Google Scholar]
- Kinet J. P. The high-affinity receptor for IgE. Curr Opin Immunol. 1989;2(4):499–505. doi: 10.1016/0952-7915(90)90002-x. [DOI] [PubMed] [Google Scholar]
- Letourneur F., Klausner R. D. T-cell and basophil activation through the cytoplasmic tail of T-cell-receptor zeta family proteins. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8905–8909. doi: 10.1073/pnas.88.20.8905. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Letourneur O., Kennedy I. C., Brini A. T., Ortaldo J. R., O'Shea J. J., Kinet J. P. Characterization of the family of dimers associated with Fc receptors (Fc epsilon RI and Fc gamma RIII). J Immunol. 1991 Oct 15;147(8):2652–2656. [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]
- 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]
- Park D. J., Min H. K., Rhee S. G. IgE-induced tyrosine phosphorylation of phospholipase C-gamma 1 in rat basophilic leukemia cells. J Biol Chem. 1991 Dec 25;266(36):24237–24240. [PubMed] [Google Scholar]
- Ravetch J. V., Kinet J. P. Fc receptors. Annu Rev Immunol. 1991;9:457–492. doi: 10.1146/annurev.iy.09.040191.002325. [DOI] [PubMed] [Google Scholar]
- Reth M. Antigen receptor tail clue. Nature. 1989 Mar 30;338(6214):383–384. doi: 10.1038/338383b0. [DOI] [PubMed] [Google Scholar]
- Reth M., Hombach J., Wienands J., Campbell K. S., Chien N., Justement L. B., Cambier J. C. The B-cell antigen receptor complex. Immunol Today. 1991 Jun;12(6):196–201. doi: 10.1016/0167-5699(91)90053-V. [DOI] [PubMed] [Google Scholar]
- Rivera J., Kinet J. P., Kim J., Pucillo C., Metzger H. Studies with a monoclonal antibody to the beta subunit of the receptor with high affinity for immunoglobulin E. Mol Immunol. 1988 Jul;25(7):647–661. doi: 10.1016/0161-5890(88)90100-9. [DOI] [PubMed] [Google Scholar]
- Romeo C., Seed B. Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides. Cell. 1991 Mar 8;64(5):1037–1046. doi: 10.1016/0092-8674(91)90327-u. [DOI] [PubMed] [Google Scholar]
- Samelson L. E., Phillips A. F., Luong E. T., Klausner R. D. Association of the fyn protein-tyrosine kinase with the T-cell antigen receptor. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4358–4362. doi: 10.1073/pnas.87.11.4358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taniguchi T., Kobayashi T., Kondo J., Takahashi K., Nakamura H., Suzuki J., Nagai K., Yamada T., Nakamura S., Yamamura H. Molecular cloning of a porcine gene syk that encodes a 72-kDa protein-tyrosine kinase showing high susceptibility to proteolysis. J Biol Chem. 1991 Aug 25;266(24):15790–15796. [PubMed] [Google Scholar]
- Veillette A., Bookman M. A., Horak E. M., Samelson L. E., Bolen J. B. Signal transduction through the CD4 receptor involves the activation of the internal membrane tyrosine-protein kinase p56lck. Nature. 1989 Mar 16;338(6212):257–259. doi: 10.1038/338257a0. [DOI] [PubMed] [Google Scholar]
- Wang B., Rieger A., Kilgus O., Ochiai K., Maurer D., Födinger D., Kinet J. P., Stingl G. Epidermal Langerhans cells from normal human skin bind monomeric IgE via Fc epsilon RI. J Exp Med. 1992 May 1;175(5):1353–1365. doi: 10.1084/jem.175.5.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weiss A., Koretzky G., Schatzman R. C., Kadlecek T. Functional activation of the T-cell antigen receptor induces tyrosine phosphorylation of phospholipase C-gamma 1. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5484–5488. doi: 10.1073/pnas.88.13.5484. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yu K. T., Lyall R., Jariwala N., Zilberstein A., Haimovich J. Antigen- and ionophore-induced signal transduction in rat basophilic leukemia cells involves protein tyrosine phosphorylation. J Biol Chem. 1991 Nov 25;266(33):22564–22568. [PubMed] [Google Scholar]