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PMID: 9064320 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Fc gamma R-dependent mitogen-activated protein kinase activation in leukocytes: a common signal transduction event necessary for expression of TNF-alpha and early activation genes.

The Journal of experimental medicine ·Vol. 184 ·No. 3 ·1996-09-01 ·Pages 1027-35

Trotta R, Kanakaraj P, Perussia B

Abstract

Cross-linking the receptors for the Fc domain of IgG (Fc gamma R) on leukocytes induces activation of protein tyrosine kinases. The intermediary molecules that transduce to the nucleus the signals leading to induction of the diverse biological responses mediated by these receptors are not clearly identified. We have investigated whether mitogen-activated protein kinases (MAPK) are involved in transmembrane signaling via the three Fc gamma R present on monocytic, polymorphonuclear, and natural killer (NK) cells. Our results indicate that occupancy of Fc gamma RI and Fc gamma RII on the monocytic cell line THP-I and on polymorphonuclear leukocytes (PMN) induces, transiently and with fast kinetics, MAPK phosphorylation, as indicated by decreased electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and increased amounts of the proteins in antiphosphotyrosine antibody immunoprecipitates. This, associated with increased enzymatic activity, also occurs upon stimulation of the transmembrane isoform of CD16 (Fc gamma RIIIA) in NK cells and in a T cell line expressing transfected Fc gamma RIIIA alpha ligand-binding chain in association with zeta, but not upon stimulation of the glycosil-phosphatidylinositol-anchored Fc gamma RIIIB on PMN. Using the specific MAP kinase kinase inhibitor-PD 098059, we show that activation of MAPK is necessary for the Fc gamma R-dependent induction of c-fos and tumor necrosis factor alpha mRNA expression in monocytes and NK cells. These results underscore the role of MAPK as signal-transducing molecules controlling the expression of different genes relevant to leukocyte biology upon Fc gamma R stimulation.

MeSH Terms
Animals Calcium-Calmodulin-Dependent Protein Kinases/metabolism Electrophoresis, Polyacrylamide Gel Enzyme Activation Gene Expression Regulation, Enzymologic Humans Killer Cells, Natural/metabolism Kinetics Leukocytes/enzymology Mice Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases Phosphorylation Receptors, IgG/metabolism Signal Transduction Th1 Cells/metabolism Tumor Cells, Cultured Tumor Necrosis Factor-alpha/biosynthesis
Chemicals
Receptors, IgG Tumor Necrosis Factor-alpha Calcium-Calmodulin-Dependent Protein Kinases Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Trotta R
Kimmel Cancer Center, Department of Microbiology and Immunology, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Kanakaraj P
Perussia B
References (55)
55 references, click to expand
  1. Association of a 70-kDa tyrosine phosphoprotein with the CD16: zeta: gamma complex expressed in human natural killer cells.
    Eur J Immunol. 1993 Aug;23(8):1872-6 PMID: 8344348
  2. CD16-mediated p21ras activation is associated with Shc and p36 tyrosine phosphorylation and their binding with Grb2 in human natural killer cells.
    J Exp Med. 1996 Jan 1;183(1):179-86 PMID: 8551221
  3. Activation of multiple protein kinases including a MAP kinase upon Fc epsilon RI cross-linking.
    Int Arch Allergy Immunol. 1993;102(1):15-25 PMID: 8400883
  4. Cross-linking of Fc gamma receptor I (Fc gamma RI) and receptor II (Fc gamma RII) on monocytic cells activates a signal transduction pathway common to both Fc receptors that involves the stimulation of p72 Syk protein tyrosine kinase.
    J Biol Chem. 1993 Nov 15;268(32):24442-8 PMID: 8226994
  5. Association of all three types of Fc gamma R (CD64, CD32, and CD16) with a gamma-chain homodimer in cultured human monocytes.
    J Immunol. 1993 Dec 15;151(12):7188-95 PMID: 8258719
  6. Signal transduction by lymphocyte antigen receptors.
    Cell. 1994 Jan 28;76(2):263-74 PMID: 8293463
  7. Phosphatidylinositol-3 kinase activation induced upon Fc gamma RIIIA-ligand interaction.
    J Exp Med. 1994 Feb 1;179(2):551-8 PMID: 8294866
  8. Control of MAP kinase activation by the mitogen-induced threonine/tyrosine phosphatase PAC1.
    Nature. 1994 Feb 17;367(6464):651-4 PMID: 8107850
  9. 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):5429-37 PMID: 8189062
  10. MAP kinase kinase kinase, MAP kinase kinase and MAP kinase.
    Curr Opin Genet Dev. 1994 Feb;4(1):82-9 PMID: 8193545
  11. Physical and functional association of the high affinity immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and Lyn.
    J Exp Med. 1994 Sep 1;180(3):1165-70 PMID: 8064233
  12. The use of the avidin-biotin complex as a tool in molecular biology.
    Methods Biochem Anal. 1980;26:1-45 PMID: 7392958
  13. Terminal differentiation surface antigens of myelomonocytic cells are expressed in human promyelocytic leukemia cells (HL60) treated with chemical inducers.
    Blood. 1981 Oct;58(4):836-43 PMID: 6944113
  14. Immune interferon induces the receptor for monomeric IgG1 on human monocytic and myeloid cells.
    J Exp Med. 1983 Oct 1;158(4):1092-113 PMID: 6225822
  15. On the fragmentation of monoclonal IgG1, IgG2a, and IgG2b from BALB/c mice.
    J Immunol. 1983 Dec;131(6):2895-902 PMID: 6358356
  16. The cytotoxic effector cells in preparations of adherent mononuclear cells from human peripheral blood.
    J Immunol. 1984 Mar;132(3):1255-60 PMID: 6693767
  17. Human monocytes and U937 cells bear two distinct Fc receptors for IgG.
    J Immunol. 1986 Mar 1;136(5):1641-7 PMID: 2936805
  18. Heteroantibody-mediated cytotoxicity: antibody to the high affinity Fc receptor for IgG mediates cytotoxicity by human monocytes that is enhanced by interferon-gamma and is not blocked by human IgG.
    J Immunol. 1986 Dec 1;137(11):3378-82 PMID: 2946759
  19. Immune interferon enhances functional properties of human granulocytes: role of Fc receptors and effect of lymphotoxin, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor.
    J Immunol. 1987 Feb 1;138(3):765-74 PMID: 3100615
  20. Involvement of phosphatidylinositol 3-kinase in Fc gamma receptor signaling.
    J Biol Chem. 1994 Sep 9;269(36):22732-7 PMID: 7521331
  21. 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):1753-9 PMID: 7521687
  22. PHAS-I as a link between mitogen-activated protein kinase and translation initiation.
    Science. 1994 Oct 28;266(5185):653-6 PMID: 7939721
  23. Ras-dependent and -independent pathways target the mitogen-activated protein kinase network in macrophages.
    Mol Cell Biol. 1995 Jan;15(1):466-75 PMID: 7799956
  24. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation.
    Cell. 1995 Jan 27;80(2):179-85 PMID: 7834738
  25. Transcriptional regulation by extracellular signals: mechanisms and specificity.
    Cell. 1995 Jan 27;80(2):199-211 PMID: 7834740
  26. Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation.
    Cell. 1995 Apr 21;81(2):223-31 PMID: 7736574
  27. Preferential proliferation of natural killer cells among peripheral blood mononuclear cells cocultured with B lymphoblastoid cell lines.
    Nat Immun Cell Growth Regul. 1987;6(4):171-88 PMID: 2960890
  28. Interaction of Fc receptor (CD16) ligands induces transcription of interleukin 2 receptor (CD25) and lymphokine genes and expression of their products in human natural killer cells.
    J Exp Med. 1988 Feb 1;167(2):452-72 PMID: 2831292
  29. Fc gamma R(CD16) interaction with ligand induces Ca2+ mobilization and phosphoinositide turnover in human natural killer cells. Role of Ca2+ in Fc gamma R(CD16)-induced transcription and expression of lymphokine genes.
    J Exp Med. 1989 Feb 1;169(2):549-67 PMID: 2536067
  30. Identification of the regulatory phosphorylation sites in pp42/mitogen-activated protein kinase (MAP kinase).
    EMBO J. 1991 Apr;10(4):885-92 PMID: 1849075
  31. Fc receptors.
    Annu Rev Immunol. 1991;9:457-92 PMID: 1910686
  32. Stimulation of B-cells via the membrane immunoglobulin receptor or with phorbol myristate 13-acetate induces tyrosine phosphorylation and activation of a 42-kDa microtubule-associated protein-2 kinase.
    J Biol Chem. 1991 Oct 5;266(28):19088-94 PMID: 1655769
  33. Characterization of the family of dimers associated with Fc receptors (Fc epsilon RI and Fc gamma RIII).
    J Immunol. 1991 Oct 15;147(8):2652-6 PMID: 1833456
  34. Regulation of phagocytosis and [Ca2+]i flux by distinct regions of an Fc receptor.
    Science. 1991 Dec 20;254(5039):1785-8 PMID: 1837175
  35. Ras is essential for nerve growth factor- and phorbol ester-induced tyrosine phosphorylation of MAP kinases.
    Cell. 1992 Mar 20;68(6):1031-40 PMID: 1312392
  36. A role for protein tyrosine kinase activity in natural cytotoxicity as well as antibody-dependent cellular cytotoxicity. Effects of herbimycin A.
    J Immunol. 1992 Apr 15;148(8):2497-502 PMID: 1532816
  37. Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter.
    Nature. 1992 Jul 30;358(6385):414-7 PMID: 1322499
  38. Protein tyrosine phosphorylation induced via the IgG receptors Fc gamma Ri and Fc gamma RII in the human monocytic cell line THP-1.
    J Immunol. 1992 Sep 1;149(5):1751-7 PMID: 1387152
  39. p21ras mediates control of IL-2 gene promoter function in T cell activation.
    EMBO J. 1992 Dec;11(12):4549-56 PMID: 1425589
  40. The regulation of the human tumor necrosis factor alpha promoter region in macrophage, T cell, and B cell lines.
    J Biol Chem. 1992 Nov 5;267(31):22102-7 PMID: 1429562
  41. Stimulation of Fc gamma RIIIA results in phospholipase C-gamma 1 tyrosine phosphorylation and p56lck activation.
    J Exp Med. 1992 Dec 1;176(6):1745-50 PMID: 1281217
  42. Stimulation of tyrosine phosphorylation and calcium mobilization by Fc gamma receptor cross-linking. Regulation by the phosphotyrosine phosphatase CD45.
    J Immunol. 1993 Jan 15;150(2):605-16 PMID: 8419492
  43. cPLA2 is phosphorylated and activated by MAP kinase.
    Cell. 1993 Jan 29;72(2):269-78 PMID: 8381049
  44. Physical and functional association of p56lck with Fc gamma RIIIA (CD16) in natural killer cells.
    J Exp Med. 1993 May 1;177(5):1475-80 PMID: 8478617
  45. Human IgG Fc receptor heterogeneity: molecular aspects and clinical implications.
    Immunol Today. 1993 May;14(5):215-21 PMID: 8517920
  46. Signal transduction by Fc receptors: the Fc epsilon RI case.
    Immunol Today. 1993 May;14(5):222-6 PMID: 8517921
  47. Signal transduction via the MAP kinases: proceed at your own RSK.
    Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5889-92 PMID: 8392180
  48. Association of the high-affinity receptor for IgG (Fc gamma RI) with the gamma subunit of the IgE receptor.
    Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6023-7 PMID: 8327478
  49. Interleukin-2 triggers a novel phosphatidylinositol 3-kinase-dependent MEK activation pathway.
    Mol Cell Biol. 1995 Jun;15(6):3049-57 PMID: 7760801
  50. Distinct tyrosine kinase activation and Triton X-100 insolubility upon Fc gamma RII or Fc gamma RIIIB ligation in human polymorphonuclear leukocytes. Implications for immune complex activation of the respiratory burst.
    J Biol Chem. 1995 Jun 2;270(22):13553-60 PMID: 7768958
  51. The regulation of AP-1 activity by mitogen-activated protein kinases.
    J Biol Chem. 1995 Jul 14;270(28):16483-6 PMID: 7622446
  52. A synthetic inhibitor of the mitogen-activated protein kinase cascade.
    Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7686-9 PMID: 7644477
  53. Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding.
    J Exp Med. 1995 Sep 1;182(3):801-10 PMID: 7650486
  54. Antigen and Fc receptor signaling. The awesome power of the immunoreceptor tyrosine-based activation motif (ITAM).
    J Immunol. 1995 Oct 1;155(7):3281-5 PMID: 7561018
  55. p21ras couples the T cell antigen receptor to extracellular signal-regulated kinase 2 in T lymphocytes.
    J Exp Med. 1993 Oct 1;178(4):1199-208 PMID: 8376929
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.184.3.1027
Published
1996-09-01
Pages
1027-35
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192797
Subset
IM
Grants
NCI NIH HHS · CA-37155 · United States
NCI NIH HHS · CA-45284 · United States
NCI NIH HHS · T32-CA-09678 · United States
External Links
PubMed source DOI: 10.1084/jem.184.3.1027 PMC Full Text View journal details
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