Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils.

Hamada, Fumihiko; Aoki, Masahiro; Akiyama, Tetsu; Toyoshima, Kumao

doi:10.1073/pnas.90.13.6305

Cited by 125 publications

(67 citation statements)

References 39 publications

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“…In accordance with this supposition, Src-deficient cells are less capable of FcyRIIA-mediated phagocytosis and receptor phosphorylation [33]. In neutrophils FcyRII is associated with Fgr and the receptor cross-linking is accompanied by Fgr activation [34]. FcyRI and FcyRII in monocytic cells are physically and functionally associated with two other Src family kinases -Hck and Lyn.…”

Section: Fey-associated Tyrosine Kinasesmentioning

confidence: 82%

“…paxilin (68 kDa), a cytoskeleton-associated, Src tyrosine kinase substrate which colocalizes with F-actin beneath nascent phagosomes [15,31]. The tyrosine phosphorylated proteins of 50-60 kDa are likely to belong to the Src family kinases [34][35][36]. The polypeptide of 72 kDa has been suggested to be Syk kinase [12,15,37,40,42].…”

Section: Substrates Of Tyrosine Kinasesmentioning

confidence: 99%

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Tyrosine phosphorylation and Fcγ receptor‐mediated phagocytosis

1997

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Phagocytosis of IgG-opsonized participate material in hematopoietic cells is mediated by Fey receptors (FcyRs).Interaction of the receptors with Fc domains of IgG triggers transduction of phagocytic signal in which a key role is played by phosphorylation of tyrosine residues of the receptors. These residues are arranged into a specific motif (immunoreceptor tyrosine-based activation motif; ITAM) which is located either in the cytoplasmic part of FeyRIIA or in γchains associated with FeyRI and FcyRIIIA. The conserved tyrosine residues are phosphorylated by, and associate with, tyrosine kinases of Src and Syk families. Coordinated action of these components initiates numerous intracellular events leading finally to local rearrangement of the actin-based cytoskeleton and internalization of the particles.

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Section: Fey-associated Tyrosine Kinasesmentioning

confidence: 82%

Section: Substrates Of Tyrosine Kinasesmentioning

confidence: 99%

Tyrosine phosphorylation and Fcγ receptor‐mediated phagocytosis

1997

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“…Thus, Fgr seems to be specifically expressed in cells involved in natural immunity. Although Fgr was shown to be associated with FcyRII in neutrophils in human system (15), and with Ly6C and p70 in a macrophage cell line in murine system (17), little has been known on functional roles of the Fgr in these cells which may be related to recognition of foreign substances in a relatively nonspecific manner.…”

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confidence: 99%

Fgr Expression Restricted to Subpopulation of Monocyte/Macrophage Lineage in Resting Conditions Is Induced in Various Hematopoietic Cells after Activation or Transformation

Hatakeyama

Iwabuchi

Ato

et al. 1996

Microbiology and Immunology

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The c‐fgr gene product (Fgr) is a member of the src‐family of protein tyrosine kinases. We have established a monoclonal antibody (2H2) which recognizes the unique N‐terminal domain of the murine Fgr. In the present study, using immunohistochemical analysis and immune complex kinase assay with the 2H2, we investigated expression of Fgr in various cell populations and tissues in a murine system. In resting conditions, Fgr expression was confined to subsets of a monocyte/macrophage lineage. Thus, Fgr+ cells were detected in paracortical areas and medullas of lymph nodes, but seen only in marginal zones of the spleen and the medulla of the thymus. No Fgr+ macrophage was detected in other tissues, Peyer's patches, brain, heart, lung, liver, pancreas, kidney and peritoneal cavity. However, immune complex kinase assay revealed that, upon stimulation, T and B cells as well as peritoneal macrophages expressed significant levels of Fgr molecules. Transformed cell lines of lymphoid origin, EL‐4 and LK35.2, which are T and B lineage lymphomas, respectively, also expressed Fgr molecules. Thus, various cells of hematopoietic origin appeared to possess a potentiality to express Fgr following activation or transformation. The present findings may help elucidate the functional significance of Fgr in immunologically committed cells in either activated or non‐activated conditions.

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“…The inhibitory activity of pertussis toxin in the FMLP-ADCC system can conceivably involve inhibition of toxin-sensitive and FMLP receptor-coupled G-proteins (Snyderman and Uhing, 1992). As neither TNF-α-dependent cell stimulation nor β 2 -integrin signalling are known to involve pertussis toxin-sensitive pathways (Dinarello, 1992;Hynes, 1992), the inhibitory activity of the toxin in the TNF-α-dependent ADCC system might be attributed to the blockade of the pertussin toxinsensitive src-like tyrosine kinase fgr pathway which has been previously shown to be associated with the FcγRII signal transduction (Hamada et al, 1993;Zhou et al, 1995). This FcγR has been indeed shown to initiate transmembrane signals that can involve pertussis toxin-sensitive pathways (Gresham et al, 1987;Feister et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

FMLP- and TNF-stimulated monoclonal Lym-1 antibody-dependent lysis of B lymphoblastoid tumour targets by neutrophils

et al. 1999

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Human neutrophils, incubated with Cr 51 -labelled B lymphoblastoid Raji cells in the presence of the anti-target monoclonal antibody (mAb) Lym-1 plus formyl-methionyl-leucyl-phenylalanine (FMLP) or tumour necrosis factor alpha (TNF-α), were found to induce significant Cr 51 release, i.e. significant cytolysis. The lytic process was inhibited by mAb IV.3, specific for the Fcγ receptor (FcγR) type II. The mAb 3G8, which reacts with FcγR type III, was ineffective. Moreover, the lysis was inhibited by the anti-CD18 mAb MEM-48. These data suggest that FMLP/Lym-1 as well as TNF-α/Lym-1 cytolytic systems strictly require FcγRII and CD18 integrins. As the lysis induced by TNF-α/Lym-1 was prevented by pertussis toxin (PT), PT-sensitive G-proteins are likely to intervene in post-FcγRII signal transduction. Both the FMLP- and the TNF-α-dependent systems were also found to be equally susceptible to inhibition by various inhibitors of kinases (genistein, staurosporin, 1-(5-isoquinolinnylsulphonyl)-2-methylpiperazine and wortmannin). On the contrary, an inhibitor of protein kinase C (bis-indolyl-maleimide, BIM) was effective only in the FMLP/Lym-1 cytolytic system. Therefore, it appears that signals delivered by FMLP or TNF-α, BIM-sensitive and insensitive respectively, converge and synergize with those from G-protein-coupled FcγRII and, probably, CD18-integrins to promote the expression of the neutrophil cytolytic potential. © 1999 Cancer Research Campaign

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Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils.

Abstract: The

Cited by 125 publications

References 39 publications

Tyrosine phosphorylation and Fcγ receptor‐mediated phagocytosis

Tyrosine phosphorylation and Fcγ receptor‐mediated phagocytosis

Fgr Expression Restricted to Subpopulation of Monocyte/Macrophage Lineage in Resting Conditions Is Induced in Various Hematopoietic Cells after Activation or Transformation

FMLP- and TNF-stimulated monoclonal Lym-1 antibody-dependent lysis of B lymphoblastoid tumour targets by neutrophils

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