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J Exp Med. Sep 1, 1994; 180(3): 1165–1170.
PMCID: PMC2191633

Physical and functional association of the high affinity immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and Lyn

Abstract

The high affinity immunoglobulin G (IgG) receptor Fc gamma RI (CD64) is expressed constitutively on monocytes and macrophages, and is inducible on neutrophils. Fc gamma RI has recently been shown to be associated with the signal transducing gamma subunit of the high-affinity IgE receptor (Fc epsilon RI gamma). Induction of cytoplasmic protein tyrosine phosphorylation by Fc gamma RI cross-linking is known to be important in mediating Fc gamma RI-coupled effector functions. Recently, syk has been implicated in this role. We now report that the src-type kinases hck and lyn are physically and functionally associated with Fc gamma RI. Hck and lyn coimmunoprecipitated with Fc gamma RI from detergent lysates of normal human monocytes and of the monocytic line THP-1. Hck and lyn showed rapidly increased phosphorylation and increased exogenous substrate kinase activity after cross-linking of Fc gamma RI. These results demonstrate both physical and functional association of the Fc gamma RI/Fc epsilon RI gamma receptor complex with hck and lyn, and suggest a potential signal transducing role for these kinases in monocyte/macrophage activation.

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Selected References

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  • Canfield SM, Morrison SL. The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region. J Exp Med. 1991 Jun 1;173(6):1483–1491. [PMC free article] [PubMed]
  • Ernst LK, van de Winkel JG, Chiu IM, Anderson CL. Three genes for the human high affinity Fc receptor for IgG (Fc gamma RI) encode four distinct transcription products. J Biol Chem. 1992 Aug 5;267(22):15692–15700. [PubMed]
  • Ravetch JV, Kinet JP. Fc receptors. Annu Rev Immunol. 1991;9:457–492. [PubMed]
  • Liao F, Shin HS, Rhee SG. Tyrosine phosphorylation of phospholipase C-gamma 1 induced by cross-linking of the high-affinity or low-affinity Fc receptor for IgG in U937 cells. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3659–3663. [PMC free article] [PubMed]
  • Scholl PR, Ahern D, Geha RS. 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):1751–1757. [PubMed]
  • Yamanashi Y, Kakiuchi T, Mizuguchi J, Yamamoto T, Toyoshima K. Association of B cell antigen receptor with protein tyrosine kinase Lyn. Science. 1991 Jan 11;251(4990):192–194. [PubMed]
  • Samelson LE, Phillips AF, Luong ET, Klausner RD. 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. [PMC free article] [PubMed]
  • Glaichenhaus N, Shastri N, Littman DR, Turner JM. Requirement for association of p56lck with CD4 in antigen-specific signal transduction in T cells. Cell. 1991 Feb 8;64(3):511–520. [PubMed]
  • Veillette A, Bookman MA, Horak EM, Bolen JB. 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. [PubMed]
  • Einspahr KJ, Abraham RT, Binstadt BA, Uehara Y, Leibson PJ. Tyrosine phosphorylation provides an early and requisite signal for the activation of natural killer cell cytotoxic function. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6279–6283. [PMC free article] [PubMed]
  • Scholl PR, Geha RS. Physical association between the high-affinity IgG receptor (Fc gamma RI) and the gamma subunit of the high-affinity IgE receptor (Fc epsilon RI gamma). Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8847–8850. [PMC free article] [PubMed]
  • Ernst LK, Duchemin AM, Anderson CL. 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):6023–6027. [PMC free article] [PubMed]
  • Masuda M, Roos D. 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):7188–7195. [PubMed]
  • Wirthmueller U, Kurosaki T, Murakami MS, Ravetch JV. Signal transduction by Fc gamma RIII (CD16) is mediated through the gamma chain. J Exp Med. 1992 May 1;175(5):1381–1390. [PMC free article] [PubMed]
  • Qian D, Sperling AI, Lancki DW, Tatsumi Y, Barrett TA, Bluestone JA, Fitch FW. The gamma chain of the high-affinity receptor for IgE is a major functional subunit of the T-cell antigen receptor complex in gamma delta T lymphocytes. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11875–11879. [PMC free article] [PubMed]
  • Reth M. Antigen receptor tail clue. Nature. 1989 Mar 30;338(6214):383–384. [PubMed]
  • Bolen JB. Signal transduction by the SRC family of tyrosine protein kinases in hemopoietic cells. Cell Growth Differ. 1991 Aug;2(8):409–414. [PubMed]
  • Quintrell N, Lebo R, Varmus H, Bishop JM, Pettenati MJ, Le Beau MM, Diaz MO, Rowley JD. Identification of a human gene (HCK) that encodes a protein-tyrosine kinase and is expressed in hemopoietic cells. Mol Cell Biol. 1987 Jun;7(6):2267–2275. [PMC free article] [PubMed]
  • Ziegler SF, Marth JD, Lewis DB, Perlmutter RM. Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells of hematopoietic origin. Mol Cell Biol. 1987 Jun;7(6):2276–2285. [PMC free article] [PubMed]
  • Boulet I, Ralph S, Stanley E, Lock P, Dunn AR, Green SP, Phillips WA. Lipopolysaccharide- and interferon-gamma-induced expression of hck and lyn tyrosine kinases in murine bone marrow-derived macrophages. Oncogene. 1992 Apr;7(4):703–710. [PubMed]
  • English BK, Ihle JN, Myracle A, Yi T. Hck tyrosine kinase activity modulates tumor necrosis factor production by murine macrophages. J Exp Med. 1993 Sep 1;178(3):1017–1022. [PMC free article] [PubMed]
  • Burkhardt AL, Brunswick M, Bolen JB, Mond JJ. 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. [PMC free article] [PubMed]
  • Campbell MA, Sefton BM. Association between B-lymphocyte membrane immunoglobulin and multiple members of the Src family of protein tyrosine kinases. Mol Cell Biol. 1992 May;12(5):2315–2321. [PMC free article] [PubMed]
  • Clark MR, Campbell KS, Kazlauskas A, Johnson SA, Hertz M, Potter TA, Pleiman C, Cambier JC. The B cell antigen receptor complex: association of Ig-alpha and Ig-beta with distinct cytoplasmic effectors. Science. 1992 Oct 2;258(5079):123–126. [PubMed]
  • Morio T, Geha RS, Chatila TA. Engagement of MHC class II molecules by staphylococcal superantigens activates src-type protein tyrosine kinases. Eur J Immunol. 1994 Mar;24(3):651–658. [PubMed]
  • Schöneich JT, Wilkinson VL, Kado-Fong H, Presky DH, Kochan JP. Association of the human Fc epsilon RI gamma subunit with novel cell surface polypeptides. J Immunol. 1992 Apr 1;148(7):2181–2185. [PubMed]
  • Chatila T, Wong R, Young M, Miller R, Terhorst C, Geha RS. An immunodeficiency characterized by defective signal transduction in T lymphocytes. N Engl J Med. 1989 Mar 16;320(11):696–702. [PubMed]
  • Pike LJ, Gallis B, Casnellie JE, Bornstein P, Krebs EG. Epidermal growth factor stimulates the phosphorylation of synthetic tyrosine-containing peptides by A431 cell membranes. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1443–1447. [PMC free article] [PubMed]
  • Akerley WL, 3rd, Guyre PM, Davis BH. Neutrophil activation through high-affinity Fc gamma receptor using a monomeric antibody with unique properties. Blood. 1991 Feb 1;77(3):607–615. [PubMed]
  • Yi TL, Bolen JB, Ihle JN. Hematopoietic cells express two forms of lyn kinase differing by 21 amino acids in the amino terminus. Mol Cell Biol. 1991 May;11(5):2391–2398. [PMC free article] [PubMed]
  • Indik Z, Kelly C, Chien P, Levinson AI, Schreiber AD. 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. [PMC free article] [PubMed]
  • Lock P, Ralph S, Stanley E, Boulet I, Ramsay R, Dunn AR. Two isoforms of murine hck, generated by utilization of alternative translational initiation codons, exhibit different patterns of subcellular localization. Mol Cell Biol. 1991 Sep;11(9):4363–4370. [PMC free article] [PubMed]
  • Davidson D, Chow LM, Fournel M, Veillette A. Differential regulation of T cell antigen responsiveness by isoforms of the src-related tyrosine protein kinase p59fyn. J Exp Med. 1992 Jun 1;175(6):1483–1492. [PMC free article] [PubMed]
  • Yamanashi Y, Miyasaka M, Takeuchi M, Ilic D, Mizuguchi J, Yamamoto T. Differential responses of p56lyn and p53lyn, products of alternatively spliced lyn mRNA, on stimulation of B-cell antigen receptor. Cell Regul. 1991 Dec;2(12):979–987. [PMC free article] [PubMed]
  • Rider LG, Raben N, Miller L, Jelsema C. The cDNAs encoding two forms of the LYN protein tyrosine kinase are expressed in rat mast cells and human myeloid cells. Gene. 1994 Jan 28;138(1-2):219–222. [PubMed]
  • Shaw AS, Amrein KE, Hammond C, Stern DF, Sefton BM, Rose JK. The lck tyrosine protein kinase interacts with the cytoplasmic tail of the CD4 glycoprotein through its unique amino-terminal domain. Cell. 1989 Nov 17;59(4):627–636. [PubMed]
  • Agarwal A, Salem P, Robbins KC. Involvement of p72syk, a protein-tyrosine kinase, in Fc gamma receptor signaling. J Biol Chem. 1993 Jul 25;268(21):15900–15905. [PubMed]
  • Kiener PA, Rankin BM, Burkhardt AL, Schieven GL, Gilliland LK, Rowley RB, Bolen JB, Ledbetter JA. 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):24442–24448. [PubMed]
  • Benhamou M, Ryba NJ, Kihara H, Nishikata H, Siraganian RP. 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 Nov 5;268(31):23318–23324. [PubMed]
  • Jouvin MH, Adamczewski M, Numerof R, Letourneur O, Vallé A, Kinet JP. 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]

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