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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Oct 11;91(21):10232–10236. doi: 10.1073/pnas.91.21.10232

Transfection of an Fc gamma receptor cDNA induces T cells to become phagocytic.

S Hunter 1, M Kamoun 1, A D Schreiber 1
PMCID: PMC44992  PMID: 7937868

Abstract

The human receptor Fc gamma RIIA for the Fc portion of IgG (Fc gamma) was expressed in a human T-cell line and conferred on these cells the ability to perform IgG antibody-stimulated phagocytosis. Crosslinking Fc gamma RIIA with anti-Fc gamma RII monoclonal antibody also induced tyrosine phosphorylation of multiple proteins including Fc gamma RIIA, ZAP-70, p72SYK, and phospholipase C gamma 1 subunit and an increase in intracellular Ca2+ concentration. The T cell receptor-associated zeta-chain was not tyrosine-phosphorylated after crosslinking of Fc gamma RIIA, suggesting that the Fc gamma RIIA-mediated signals were independent of CD3. Fc gamma RIIA-mediated signal transduction was defective in a transfected mutant T-cell line exhibiting reduced expression of the tyrosine kinases LCK and FYN. These studies indicate that certain T cells can assume phagocytic properties after transfection of cDNA encoding an Fc gamma receptor with the capability of inducing a phagocytic signal.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agarwal A., Salem P., Robbins K. C. Involvement of p72syk, a protein-tyrosine kinase, in Fc gamma receptor signaling. J Biol Chem. 1993 Jul 25;268(21):15900–15905. [PubMed] [Google Scholar]
  2. Azzoni L., Kamoun M., Salcedo T. W., Kanakaraj P., Perussia B. Stimulation of Fc gamma RIIIA results in phospholipase C-gamma 1 tyrosine phosphorylation and p56lck activation. J Exp Med. 1992 Dec 1;176(6):1745–1750. doi: 10.1084/jem.176.6.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bolen J. B. Signal transduction by the SRC family of tyrosine protein kinases in hemopoietic cells. Cell Growth Differ. 1991 Aug;2(8):409–414. [PubMed] [Google Scholar]
  4. Chan A. C., Iwashima M., Turck C. W., Weiss A. ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. Cell. 1992 Nov 13;71(4):649–662. doi: 10.1016/0092-8674(92)90598-7. [DOI] [PubMed] [Google Scholar]
  5. Darby C., Geahlen R. L., Schreiber A. D. Stimulation of macrophage Fc gamma RIIIA activates the receptor-associated protein tyrosine kinase Syk and induces phosphorylation of multiple proteins including p95Vav and p62/GAP-associated protein. J Immunol. 1994 Jun 1;152(11):5429–5437. [PubMed] [Google Scholar]
  6. Fanger M. W., Shen L., Graziano R. F., Guyre P. M. Cytotoxicity mediated by human Fc receptors for IgG. Immunol Today. 1989 Mar;10(3):92–99. doi: 10.1016/0167-5699(89)90234-X. [DOI] [PubMed] [Google Scholar]
  7. Greaves D. R., Wilson F. D., Lang G., Kioussis D. Human CD2 3'-flanking sequences confer high-level, T cell-specific, position-independent gene expression in transgenic mice. Cell. 1989 Mar 24;56(6):979–986. doi: 10.1016/0092-8674(89)90631-4. [DOI] [PubMed] [Google Scholar]
  8. Hamada F., Aoki M., Akiyama T., Toyoshima K. Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6305–6309. doi: 10.1073/pnas.90.13.6305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hibbs M. L., Bonadonna L., Scott B. M., McKenzie I. F., Hogarth P. M. Molecular cloning of a human immunoglobulin G Fc receptor. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2240–2244. doi: 10.1073/pnas.85.7.2240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huang M. M., Indik Z., Brass L. F., Hoxie J. A., Schreiber A. D., Brugge J. S. Activation of Fc gamma RII induces tyrosine phosphorylation of multiple proteins including Fc gamma RII. J Biol Chem. 1992 Mar 15;267(8):5467–5473. [PubMed] [Google Scholar]
  11. Hunter S., Huang M. M., Indik Z. K., Schreiber A. D. Fc gamma RIIA-mediated phagocytosis and receptor phosphorylation in cells deficient in the protein tyrosine kinase Src. Exp Hematol. 1993 Oct;21(11):1492–1497. [PubMed] [Google Scholar]
  12. 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]
  13. Indik Z. K., Pan X. Q., Huang M. M., McKenzie S. E., Levinson A. I., Schreiber A. D. Insertion of cytoplasmic tyrosine sequences into the nonphagocytic receptor Fc gamma RIIB establishes phagocytic function. Blood. 1994 Apr 15;83(8):2072–2080. [PubMed] [Google Scholar]
  14. Indik Z., Kelly C., Chien P., Levinson A. I., Schreiber A. D. Human Fc gamma RII, in the absence of other Fc gamma receptors, mediates a phagocytic signal. J Clin Invest. 1991 Nov;88(5):1766–1771. doi: 10.1172/JCI115496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lang G., Wotton D., Owen M. J., Sewell W. A., Brown M. H., Mason D. Y., Crumpton M. J., Kioussis D. The structure of the human CD2 gene and its expression in transgenic mice. EMBO J. 1988 Jun;7(6):1675–1682. doi: 10.1002/j.1460-2075.1988.tb02995.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mitchell M. A., Huang M. M., Chien P., Indik Z. K., Pan X. Q., Schreiber A. D. Substitutions and deletions in the cytoplasmic domain of the phagocytic receptor Fc gamma RIIA: effect on receptor tyrosine phosphorylation and phagocytosis. Blood. 1994 Sep 15;84(6):1753–1759. [PubMed] [Google Scholar]
  17. 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]
  18. Park D. J., Rho H. W., Rhee S. G. CD3 stimulation causes phosphorylation of phospholipase C-gamma 1 on serine and tyrosine residues in a human T-cell line. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5453–5456. doi: 10.1073/pnas.88.12.5453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Qiu W. Q., de Bruin D., Brownstein B. H., Pearse R., Ravetch J. V. Organization of the human and mouse low-affinity Fc gamma R genes: duplication and recombination. Science. 1990 May 11;248(4956):732–735. doi: 10.1126/science.2139735. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Romeo C., Amiot M., Seed B. Sequence requirements for induction of cytolysis by the T cell antigen/Fc receptor zeta chain. Cell. 1992 Mar 6;68(5):889–897. doi: 10.1016/0092-8674(92)90032-8. [DOI] [PubMed] [Google Scholar]
  22. Salcedo T. W., Kurosaki T., Kanakaraj P., Ravetch J. V., Perussia B. Physical and functional association of p56lck with Fc gamma RIIIA (CD16) in natural killer cells. J Exp Med. 1993 May 1;177(5):1475–1480. doi: 10.1084/jem.177.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Sancho J., Peter M. E., Franco R., Danielian S., Kang J. S., Fagard R., Woods J., Reed J. C., Kamoun M., Terhorst C. Coupling of GTP-binding to the T cell receptor (TCR) zeta-chain with TCR-mediated signal transduction. J Immunol. 1993 Apr 15;150(8 Pt 1):3230–3242. [PubMed] [Google Scholar]
  25. Sandor M., Cook G. A., Sacco R. E., Mathew R., Ibraghimov A., Weinstock J. V., Lynch R. G. TCR induced expression of Fc receptors on murine T cell subsets in vitro and in vivo. Immunobiology. 1992 Aug;185(2-4):268–280. doi: 10.1016/S0171-2985(11)80645-5. [DOI] [PubMed] [Google Scholar]
  26. Sandor M., Lynch R. G. Lymphocyte Fc receptors: the special case of T cells. Immunol Today. 1993 May;14(5):227–231. doi: 10.1016/0167-5699(93)90168-K. [DOI] [PubMed] [Google Scholar]
  27. Secrist J. P., Karnitz L., Abraham R. T. T-cell antigen receptor ligation induces tyrosine phosphorylation of phospholipase C-gamma 1. J Biol Chem. 1991 Jul 5;266(19):12135–12139. [PubMed] [Google Scholar]
  28. 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]
  29. Tsygankov A. Y., Kim H. W., Pratt J. C., Spana C., Class K., Gaulton G. N., Kamoun M., Bolen J. B. Diminished tyrosine protein kinase activity in T cells unresponsive to TCR stimulation. J Leukoc Biol. 1994 Mar;55(3):289–298. doi: 10.1002/jlb.55.3.289. [DOI] [PubMed] [Google Scholar]
  30. Wirthmueller U., Kurosaki T., Murakami M. S., Ravetch J. V. Signal transduction by Fc gamma RIII (CD16) is mediated through the gamma chain. J Exp Med. 1992 May 1;175(5):1381–1390. doi: 10.1084/jem.175.5.1381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. van de Winkel J. G., Anderson C. L. Biology of human immunoglobulin G Fc receptors. J Leukoc Biol. 1991 May;49(5):511–524. doi: 10.1002/jlb.49.5.511. [DOI] [PubMed] [Google Scholar]

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