DOI: 10.1084/jem.191.3.515. Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr

Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr

10.1084/jem.191.3.515

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

Ingestion of opsonized pathogens by professional phagocytes results in the generation and release of microbicidal products that are essential for normal host defense. Because these products can result in significant tissue injury, phagocytosis must be regulated to limit damage to the host while allowing for optimal clearance and destruction of opsonized pathogens. To pursue negative regulation of phagocytosis, we assessed the effect of the Src kinase family member, Fgr, on opsonin-dependent phagocytosis by mouse macrophages. We chose Fgr because it is present in high concentrations in circulating phagocytes but is not essential for Fcγ receptor–mediated ingestion by mouse macrophages. Although expression of Fgr both in a macrophage cell line and in primary macrophages significantly attenuates ingestion mediated by Fcγ receptors and CR3, it does not affect macropinocytosis or receptor-mediated endocytosis. This selective effect of Fgr is independent of its tyrosine kinase function. After Fcγ receptor cross-linking, Fgr becomes associated with the immunoreceptor tyrosine-based inhibition motif (ITIM)–containing receptor, SIRPα (a member of the signal-regulatory protein family, also known as Src homology 2 domain–containing protein tyrosine phosphatase [SHP] substrate 1 [SHPS-1], brain immunoglobulin-like molecule with tyrosine-based activation motifs [BIT], and P84) and potentiates the association of the phosphatase SHP-1 with SIRPα. This association is responsible, at least in part, for decreasing positive signaling essential for optimal phagocytosis. These data demonstrate an important negative regulatory role for this Src kinase family member and suggest that this homeostatic function must be overcome for optimal uptake and clearance of opsonized pathogens.

Bibliography

Gresham, H. D., Dale, B. M., Potter, J. W., Chang, P. W., Vines, C. M., Lowell, C. A., Lagenaur, C. F., & Willman, C. L. (2000). Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr. The Journal of Experimental Medicine, 191(3), 515â528.

Authors 8

Hattie D. Gresham (first)
Benjamin M. Dale (additional)
Jeffrey W. Potter (additional)
Peter W. Chang (additional)
Charlotte M. Vines (additional)
Clifford A. Lowell (additional)
Carl F. Lagenaur (additional)
Cheryl L. Willman (additional)

References 59 Referenced 85

{'key': '2023072509092903700_R1', 'first-page': '941', 'article-title': 'Phagocytosis', 'volume-title': 'Fundamental Immunology', 'author': 'Greenberg', 'year': '1993', 'edition': '3rd ed'} / Fundamental Immunology / Phagocytosis by Greenberg (1993)
10.1002/bies.950170206 / Bioessays. / Phagocytosis by Brown (1995)
10.1146/annurev.immunol.17.1.593 / Annu. Rev. Immunol. / Mechanisms of phagocytosis by Aderem (1999)
10.1084/jem.156.4.1149 / J. Exp. Med. / Tumor-promoting phorbol esters stimulate C3b and C3bi receptor–mediated phagocytosis in cultured human monocytes by Wright (1982)
10.1016/S0021-9258(19)39003-9 / J. Biol. Chem. / Studies on the molecular mechanisms of human neutrophil Fc receptor-mediated phagocytosis by Gresham (1990)
10.1172/JCI115343 / J. Clin. Invest. / Leukocyte adhesion–deficient neutrophils fail to amplify phagocytic function in response to stimulationevidence for CD11b/CD18-dependent and -independent mechanisms of phagocytosis by Gresham (1991)
10.1083/jcb.108.5.1935 / J. Cell Biol. / A novel member of the integrin receptor family mediates Arg-Gly-Asp–stimulated neutrophil phagocytosis by Gresham (1989)
10.1074/jbc.271.48.30587 / J. Biol. Chem. / Domain-specific interactions between entactin and neutrophil integrins by Gresham (1996)
10.4049/jimmunol.162.12.7041 / J. Immunol. / Reactive oxygen intermediates enhance Fcγ receptor signaling and amplify phagocytic capacity by Pricop (1999)
10.1126/science.280.5361.243 / Science. / Homeostasis and self-tolerance in the immune systemturning lymphocytes off by Parijs (1998)
10.1038/379346a0 / Nature. / Augmented humoral and anaphylactic responses in FcγRII-deficient mice by Takai (1996)
10.1084/jem.189.1.179 / J. Exp. Med. / Modulation of immune complex–induced inflammation in vivo by the coordinate expression of activation and inhibiting Fc receptors by Clynes (1999)
10.1016/0092-8674(93)80068-P / Cell. / Interleukin 10-deficient mice develop chronic enterocolitis by Kuhn (1993)
10.4049/jimmunol.155.6.3205 / J. Immunol. / SLE-like autoantibodies and Sjogren's syndrome-like lymphoproliferation in TGFβ knockout mice by Dang (1995)
10.1038/359693a0 / Nature. / Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease by Shull (1992)
10.1073/pnas.90.2.770 / Proc. Natl. Acad. Sci. USA. / Transforming growth factor-β1 null mutation in mice causes excessive inflammatory response and early death by Kulkarni (1993)
10.1016/S1074-7613(00)80554-3 / Immunity. / Polygenic autoimmune traitsLyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection by Cornall (1997)
10.1083/jcb.109.6.3129 / J. Cell Biol. / Expression of the fgr protooncogene product as a function of myelomonocytic cell maturation by Notario (1989)
10.1182/blood.V77.4.726.726 / Blood. / Expression of the c-fgr and hck protein tyrosine kinases in acute myeloid leukemic blasts is associated with early commitment and differentiation events in the monocytic and granulocytic lineages by Willman (1991)
10.1073/pnas.84.13.4480 / Proc. Natl. Acad. Sci. USA. / Differential expression and regulation of the c-src and c-fgr protooncogenes in myelomonocytic cells by Willman (1987)
10.1073/pnas.90.13.6305 / Proc. Natl. Acad. Sci. USA. / Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils. 1993 by Hamada (1993)
10.1101/gad.8.4.387 / Genes Dev. / Functional overlap in the src gene familyinactivation of hck and fgr impairs natural immunity by Lowell (1994)
10.1016/0012-1606(90)90249-I / Dev. Biol. / Central nervous system antigen P84 can serve as a substrate for neutrite outgrowth by Chuang (1990)
10.1002/jcp.1041300316 / J. Cell. Physiol. / Isolation and characterization of a cloned growth factor dependent macrophage cell line, BAC1.2F5 by Morgan (1987)
{'key': '2023072509092903700_R25', 'first-page': '1081', 'article-title': 'Cloning of the murine c-fgr proto-oncogene cDNA and induction of c-fgr expression by proliferation and activation factors in normal bone marrow-derived monocytic cells', 'volume': '4', 'author': 'Yi', 'year': '1989', 'journal-title': 'Oncogene.'} / Oncogene. / Cloning of the murine c-fgr proto-oncogene cDNA and induction of c-fgr expression by proliferation and activation factors in normal bone marrow-derived monocytic cells by Yi (1989)
10.1016/0092-8674(83)90344-6 / Cell / Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus by Mann (1983)
10.1172/JCI119068 / J. Clin. Invest. / Intracellular demonstration of active TGFβ1 in B cells and plasma cells of autoimmune miceIgG-bound TGFβ1 suppresses neutrophil function and host defense against Staphylococcus aureus infection by Caver (1996)
10.1016/S0960-9822(06)00188-6 / Curr. Biol. / CD45 regulates Src family member kinase activity associated with macrophage integrin-mediated adhesion by Roach (1997)
10.1083/jcb.135.5.1249 / J. Cell Biol. / A role for phosphoinoside 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages by Araki (1996)
10.1074/jbc.272.33.20332 / J. Biol. Chem. / The actin cytoskeleton is required for receptor-mediated endocytosis in mammalian cells by Lamaze (1997)
{'key': '2023072509092903700_R31', 'first-page': '757', 'article-title': 'Ca2+-independent F-actin assembly and disassembly during Fc receptor–mediated phagocytosis in mouse macrophages', 'volume': '113', 'author': 'Greenberg', 'year': '1991', 'journal-title': 'J. Exp. Med.'} / J. Exp. Med. / Ca2+-independent F-actin assembly and disassembly during Fc receptor–mediated phagocytosis in mouse macrophages by Greenberg (1991)
10.1084/jem.172.6.1853 / J. Exp. Med. / Colocalization of F-actin and talin during Fc receptor–mediated phagocytosis in mouse macrophages by Greenberg (1990)
10.1084/jem.184.2.627 / J. Exp. Med. / Molecular definition of distinct cytoskeletal structures involved in complement- and Fc receptor-mediated phagocytosis in macrophages by Allen (1996)
10.1084/jem.186.7.1027 / J. Exp. Med. / A critical role for syk in signal transduction and phagocytosis mediated by Fcγ receptors on macrophages by Crowley (1997)
10.1128/MCB.18.7.4209 / Mol. Cell. Biol. / The syk protein tyrosine kinase is essential for Fcγ receptor signaling in macrophages and neutrophils by Kiefer (1998)
10.1016/S0962-8924(00)89101-1 / Trends Cell Biol. / Macropinocytosis by Swanson (1995)
10.1016/S0962-8924(00)88956-4 / Trends Cell Biol. / Phagocytosis by zippers and triggers by Swanson (1995)
10.1084/jem.186.6.955 / J. Exp. Med. / Rho is required for the initiation of calcium signaling and phagocytosis by Fcγ receptors in macrophages by Hackam (1997)
10.1096/fasebj.6.15.1281458 / FASEB J. / The src family of tyrosine protein kinases in hemopoietic signal transduction by Bolen (1992)
10.1016/0145-2126(95)00161-1 / Leuk. Res. / The function of src family tyrosine kinases in hematopoietic cells by Xu (1996)
10.1016/S0065-2776(08)60019-X / Adv. Immunol. / Inhibitory pathways triggered by ITIM-containing receptors by Bolland (1999)
10.1038/sj.onc.1202203 / Oncogene. / The major SHP-1-binding, tyrosine-phosphorylated protein in macrophages is a member of the KIR/LIR family and an SHP-1 substrate by Berg (1998)
10.1128/MCB.18.7.3838 / Mol. Cell. Biol. / Identification of major binding proteins and substrates for the SH2-containing protein tyrosine phosphatase SHP-1 in macrophages by Timms (1998)
10.1172/JCI5928 / J. Clin. Invest. / Switched at birtha new family for PECAM-1 by Newman (1999)
10.1038/386181a0 / Nature. / A family of proteins that inhibit signalling through tyrosine kinase receptors by Kharitonenkov (1997)
10.1006/excr.1998.4110 / Exp. Cell Res. / Size of the IgG-opsonized particles determines macrophage response during internalization by Koval (1998)
10.1084/jem.187.8.1343 / J. Exp. Med / A double-edged kinase Lyna positive and negative regulator for antigen receptor–mediated signals by Nishizumi (1998)
10.1016/S1074-7613(00)80511-7 / Immunity. / Characterization of the B lymphocyte populations in lyn-deficient mice and the role of lyn in signal initiation and down-regulation by Chan (1997)
10.1182/blood.V91.5.1762 / Blood. / Inhibition of Fcγ receptor-mediated phagocytosis by a nonphagocytic Fcγ receptor by Hunter (1998)
10.1074/jbc.274.2.559 / J. Biol. Chem. / Integrin-associated protein is a ligand for the P84 neural adhesion molecule by Jiang (1999)
10.1083/jcb.111.6.2785 / J. Cell Biol. / Integrin-associated proteina 50-kD plasma membrane antigen physically and functionally associated with integrins by Brown (1990)
10.1046/j.1365-2567.1997.00367.x / Immunology. / The role of the Fgr tyrosine kinase in the control of the adhesive properties of U937 monoblastoid cells and their derivatives by Faulkner (1997)
10.1073/pnas.86.22.8783 / Proc. Natl. Acad. Sci. USA. / Translocation of the Fgr protein-tyrosine kinase as a consequence of neutrophil activation by Gutkind (1989)
10.1016/S0167-4889(97)00034-7 / Biochem. Biophys. Acta. / Influence of tyrosine phosphorylation on protein interaction with FcγRIIA by Ibarrola (1997)
10.1083/jcb.126.4.1111 / J. Cell Biol. / β2 integrin–dependent protein tyrosine phosphorylation and activation of the Fgr protein tyrosine kinase in human neutrophils by Berton (1994)
10.1111/j.1348-0421.1996.tb03338.x / Microbiol. Immunol. / Fgr expression restricted to subpopulation of monocyte/macrophage lineage in resting conditions is induced in various hematopoietic cells after activation or transformation by Hatakeyama (1996)
10.1073/pnas.95.13.7580 / Proc. Natl. Acad. Sci. USA. / Resistance to endotoxic shock and reduced neutrophil migration in mice deficient for the src-family kinases hck and fgr by Lowell (1998)
10.1002/jlb.65.3.313 / J. Leukoc. Biol. / Integrin signal transduction in myeloid leukocytes by Lowell (1999)
10.1093/emboj/17.15.4391 / EMBO (Eur. Mol. Biol. Organ.) J. / A beta 1 integrin signalling pathway involving src-family kinases, cbl and PI-3 kinase is required for macrophage spreading and migration by Meng (1998)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:48 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 6:22 a.m.)
Indexed	1 week ago (Aug. 23, 2025, 12:58 a.m.)
Issued	25 years, 6 months ago (Feb. 7, 2000)
Published	25 years, 6 months ago (Feb. 7, 2000)
Published Print	25 years, 6 months ago (Feb. 7, 2000)

Funders 0

None

BibTeX

@article{Gresham_2000, title={Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr}, volume={191}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.191.3.515}, DOI={10.1084/jem.191.3.515}, number={3}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Gresham, Hattie D. and Dale, Benjamin M. and Potter, Jeffrey W. and Chang, Peter W. and Vines, Charlotte M. and Lowell, Clifford A. and Lagenaur, Carl F. and Willman, Cheryl L.}, year={2000}, month=feb, pages={515–528} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        23
      ]
    ],
    "date-time": "2025-08-23T04:58:59Z",
    "timestamp": 1755925139995
  },
  "reference-count": 59,
  "publisher": "Rockefeller University Press",
  "issue": "3",
  "content-domain": {
    "domain": [
      "rupress.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2000,
        2,
        7
      ]
    ]
  },
  "abstract": "<jats:p>Ingestion of opsonized pathogens by professional phagocytes results in the generation and release of microbicidal products that are essential for normal host defense. Because these products can result in significant tissue injury, phagocytosis must be regulated to limit damage to the host while allowing for optimal clearance and destruction of opsonized pathogens. To pursue negative regulation of phagocytosis, we assessed the effect of the Src kinase family member, Fgr, on opsonin-dependent phagocytosis by mouse macrophages. We chose Fgr because it is present in high concentrations in circulating phagocytes but is not essential for Fc\u03b3 receptor\u2013mediated ingestion by mouse macrophages. Although expression of Fgr both in a macrophage cell line and in primary macrophages significantly attenuates ingestion mediated by Fc\u03b3 receptors and CR3, it does not affect macropinocytosis or receptor-mediated endocytosis. This selective effect of Fgr is independent of its tyrosine kinase function. After Fc\u03b3 receptor cross-linking, Fgr becomes associated with the immunoreceptor tyrosine-based inhibition motif (ITIM)\u2013containing receptor, SIRP\u03b1 (a member of the signal-regulatory protein family, also known as Src homology 2 domain\u2013containing protein tyrosine phosphatase [SHP] substrate 1 [SHPS-1], brain immunoglobulin-like molecule with tyrosine-based activation motifs [BIT], and P84) and potentiates the association of the phosphatase SHP-1 with SIRP\u03b1. This association is responsible, at least in part, for decreasing positive signaling essential for optimal phagocytosis. These data demonstrate an important negative regulatory role for this Src kinase family member and suggest that this homeostatic function must be overcome for optimal uptake and clearance of opsonized pathogens.</jats:p>",
  "DOI": "10.1084/jem.191.3.515",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T16:48:33Z",
    "timestamp": 1027702113000
  },
  "page": "515-528",
  "update-policy": "http://dx.doi.org/10.1084/jem.crossmarkpolicy",
  "source": "Crossref",
  "is-referenced-by-count": 85,
  "title": "Negative Regulation of Phagocytosis in Murine Macrophages by the Src Kinase Family Member, Fgr",
  "prefix": "10.1084",
  "volume": "191",
  "author": [
    {
      "given": "Hattie D.",
      "family": "Gresham",
      "sequence": "first",
      "affiliation": [
        {
          "name": "aFrom the Research Service, Albuquerque Veterans Administration Medical Center, Albuquerque, New Mexico 87108"
        },
        {
          "name": "bDepartment of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, New Mexico 87131"
        }
      ]
    },
    {
      "given": "Benjamin M.",
      "family": "Dale",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "aFrom the Research Service, Albuquerque Veterans Administration Medical Center, Albuquerque, New Mexico 87108"
        },
        {
          "name": "bDepartment of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, New Mexico 87131"
        }
      ]
    },
    {
      "given": "Jeffrey W.",
      "family": "Potter",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "cDepartment of Pathology, University of New Mexico, Albuquerque, New Mexico 87131"
        }
      ]
    },
    {
      "given": "Peter W.",
      "family": "Chang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "cDepartment of Pathology, University of New Mexico, Albuquerque, New Mexico 87131"
        }
      ]
    },
    {
      "given": "Charlotte M.",
      "family": "Vines",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "cDepartment of Pathology, University of New Mexico, Albuquerque, New Mexico 87131"
        }
      ]
    },
    {
      "given": "Clifford A.",
      "family": "Lowell",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "dDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143"
        }
      ]
    },
    {
      "given": "Carl F.",
      "family": "Lagenaur",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "eDepartment of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213"
        }
      ]
    },
    {
      "given": "Cheryl L.",
      "family": "Willman",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "cDepartment of Pathology, University of New Mexico, Albuquerque, New Mexico 87131"
        }
      ]
    }
  ],
  "member": "291",
  "reference": [
    {
      "key": "2023072509092903700_R1",
      "first-page": "941",
      "article-title": "Phagocytosis",
      "volume-title": "Fundamental Immunology",
      "author": "Greenberg",
      "year": "1993",
      "edition": "3rd ed"
    },
    {
      "key": "2023072509092903700_R2",
      "doi-asserted-by": "crossref",
      "first-page": "109",
      "DOI": "10.1002/bies.950170206",
      "article-title": "Phagocytosis",
      "volume": "17",
      "author": "Brown",
      "year": "1995",
      "journal-title": "Bioessays."
    },
    {
      "key": "2023072509092903700_R3",
      "doi-asserted-by": "crossref",
      "first-page": "593",
      "DOI": "10.1146/annurev.immunol.17.1.593",
      "article-title": "Mechanisms of phagocytosis",
      "volume": "17",
      "author": "Aderem",
      "year": "1999",
      "journal-title": "Annu. Rev. Immunol."
    },
    {
      "key": "2023072509092903700_R4",
      "doi-asserted-by": "crossref",
      "first-page": "1149",
      "DOI": "10.1084/jem.156.4.1149",
      "article-title": "Tumor-promoting phorbol esters stimulate C3b and C3bi receptor\u2013mediated phagocytosis in cultured human monocytes",
      "volume": "156",
      "author": "Wright",
      "year": "1982",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509092903700_R5",
      "doi-asserted-by": "crossref",
      "first-page": "7819",
      "DOI": "10.1016/S0021-9258(19)39003-9",
      "article-title": "Studies on the molecular mechanisms of human neutrophil Fc receptor-mediated phagocytosis",
      "volume": "265",
      "author": "Gresham",
      "year": "1990",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072509092903700_R6",
      "doi-asserted-by": "crossref",
      "first-page": "588",
      "DOI": "10.1172/JCI115343",
      "article-title": "Leukocyte adhesion\u2013deficient neutrophils fail to amplify phagocytic function in response to stimulationevidence for CD11b/CD18-dependent and -independent mechanisms of phagocytosis",
      "volume": "88",
      "author": "Gresham",
      "year": "1991",
      "journal-title": "J. Clin. Invest."
    },
    {
      "key": "2023072509092903700_R7",
      "doi-asserted-by": "crossref",
      "first-page": "1935",
      "DOI": "10.1083/jcb.108.5.1935",
      "article-title": "A novel member of the integrin receptor family mediates Arg-Gly-Asp\u2013stimulated neutrophil phagocytosis",
      "volume": "108",
      "author": "Gresham",
      "year": "1989",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072509092903700_R8",
      "doi-asserted-by": "crossref",
      "first-page": "30587",
      "DOI": "10.1074/jbc.271.48.30587",
      "article-title": "Domain-specific interactions between entactin and neutrophil integrins",
      "volume": "271",
      "author": "Gresham",
      "year": "1996",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072509092903700_R9",
      "doi-asserted-by": "crossref",
      "first-page": "7041",
      "DOI": "10.4049/jimmunol.162.12.7041",
      "article-title": "Reactive oxygen intermediates enhance Fc\u03b3 receptor signaling and amplify phagocytic capacity",
      "volume": "162",
      "author": "Pricop",
      "year": "1999",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072509092903700_R10",
      "doi-asserted-by": "crossref",
      "first-page": "243",
      "DOI": "10.1126/science.280.5361.243",
      "article-title": "Homeostasis and self-tolerance in the immune systemturning lymphocytes off",
      "volume": "280",
      "author": "Parijs",
      "year": "1998",
      "journal-title": "Science."
    },
    {
      "key": "2023072509092903700_R11",
      "doi-asserted-by": "crossref",
      "first-page": "346",
      "DOI": "10.1038/379346a0",
      "article-title": "Augmented humoral and anaphylactic responses in Fc\u03b3RII-deficient mice",
      "volume": "379",
      "author": "Takai",
      "year": "1996",
      "journal-title": "Nature."
    },
    {
      "key": "2023072509092903700_R12",
      "doi-asserted-by": "crossref",
      "first-page": "179",
      "DOI": "10.1084/jem.189.1.179",
      "article-title": "Modulation of immune complex\u2013induced inflammation in vivo by the coordinate expression of activation and inhibiting Fc receptors",
      "volume": "189",
      "author": "Clynes",
      "year": "1999",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509092903700_R13",
      "doi-asserted-by": "crossref",
      "first-page": "263",
      "DOI": "10.1016/0092-8674(93)80068-P",
      "article-title": "Interleukin 10-deficient mice develop chronic enterocolitis",
      "volume": "75",
      "author": "Kuhn",
      "year": "1993",
      "journal-title": "Cell."
    },
    {
      "key": "2023072509092903700_R14",
      "doi-asserted-by": "crossref",
      "first-page": "3205",
      "DOI": "10.4049/jimmunol.155.6.3205",
      "article-title": "SLE-like autoantibodies and Sjogren's syndrome-like lymphoproliferation in TGF\u03b2 knockout mice",
      "volume": "155",
      "author": "Dang",
      "year": "1995",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072509092903700_R15",
      "doi-asserted-by": "crossref",
      "first-page": "693",
      "DOI": "10.1038/359693a0",
      "article-title": "Targeted disruption of the mouse transforming growth factor-\u03b21 gene results in multifocal inflammatory disease",
      "volume": "359",
      "author": "Shull",
      "year": "1992",
      "journal-title": "Nature."
    },
    {
      "key": "2023072509092903700_R16",
      "doi-asserted-by": "crossref",
      "first-page": "770",
      "DOI": "10.1073/pnas.90.2.770",
      "article-title": "Transforming growth factor-\u03b21 null mutation in mice causes excessive inflammatory response and early death",
      "volume": "90",
      "author": "Kulkarni",
      "year": "1993",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072509092903700_R17",
      "doi-asserted-by": "crossref",
      "first-page": "497",
      "DOI": "10.1016/S1074-7613(00)80554-3",
      "article-title": "Polygenic autoimmune traitsLyn, CD22, and SHP-1 are limiting elements of a biochemical pathway regulating BCR signaling and selection",
      "volume": "8",
      "author": "Cornall",
      "year": "1997",
      "journal-title": "Immunity."
    },
    {
      "key": "2023072509092903700_R18",
      "doi-asserted-by": "crossref",
      "first-page": "3129",
      "DOI": "10.1083/jcb.109.6.3129",
      "article-title": "Expression of the fgr protooncogene product as a function of myelomonocytic cell maturation",
      "volume": "109",
      "author": "Notario",
      "year": "1989",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072509092903700_R19",
      "doi-asserted-by": "crossref",
      "first-page": "726",
      "DOI": "10.1182/blood.V77.4.726.726",
      "article-title": "Expression of the c-fgr and hck protein tyrosine kinases in acute myeloid leukemic blasts is associated with early commitment and differentiation events in the monocytic and granulocytic lineages",
      "volume": "77",
      "author": "Willman",
      "year": "1991",
      "journal-title": "Blood."
    },
    {
      "key": "2023072509092903700_R20",
      "doi-asserted-by": "crossref",
      "first-page": "4480",
      "DOI": "10.1073/pnas.84.13.4480",
      "article-title": "Differential expression and regulation of the c-src and c-fgr protooncogenes in myelomonocytic cells",
      "volume": "84",
      "author": "Willman",
      "year": "1987",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072509092903700_R21",
      "doi-asserted-by": "crossref",
      "first-page": "6305",
      "DOI": "10.1073/pnas.90.13.6305",
      "article-title": "Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils. 1993",
      "volume": "90",
      "author": "Hamada",
      "year": "1993",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072509092903700_R22",
      "doi-asserted-by": "crossref",
      "first-page": "387",
      "DOI": "10.1101/gad.8.4.387",
      "article-title": "Functional overlap in the src gene familyinactivation of hck and fgr impairs natural immunity",
      "volume": "8",
      "author": "Lowell",
      "year": "1994",
      "journal-title": "Genes Dev."
    },
    {
      "key": "2023072509092903700_R23",
      "doi-asserted-by": "crossref",
      "first-page": "219",
      "DOI": "10.1016/0012-1606(90)90249-I",
      "article-title": "Central nervous system antigen P84 can serve as a substrate for neutrite outgrowth",
      "volume": "137",
      "author": "Chuang",
      "year": "1990",
      "journal-title": "Dev. Biol."
    },
    {
      "key": "2023072509092903700_R24",
      "doi-asserted-by": "crossref",
      "first-page": "420",
      "DOI": "10.1002/jcp.1041300316",
      "article-title": "Isolation and characterization of a cloned growth factor dependent macrophage cell line, BAC1.2F5",
      "volume": "130",
      "author": "Morgan",
      "year": "1987",
      "journal-title": "J. Cell. Physiol."
    },
    {
      "key": "2023072509092903700_R25",
      "first-page": "1081",
      "article-title": "Cloning of the murine c-fgr proto-oncogene cDNA and induction of c-fgr expression by proliferation and activation factors in normal bone marrow-derived monocytic cells",
      "volume": "4",
      "author": "Yi",
      "year": "1989",
      "journal-title": "Oncogene."
    },
    {
      "key": "2023072509092903700_R26",
      "doi-asserted-by": "crossref",
      "first-page": "153",
      "DOI": "10.1016/0092-8674(83)90344-6",
      "article-title": "Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus",
      "volume": "33",
      "author": "Mann",
      "year": "1983",
      "journal-title": "Cell"
    },
    {
      "key": "2023072509092903700_R27",
      "doi-asserted-by": "crossref",
      "first-page": "2496",
      "DOI": "10.1172/JCI119068",
      "article-title": "Intracellular demonstration of active TGF\u03b21 in B cells and plasma cells of autoimmune miceIgG-bound TGF\u03b21 suppresses neutrophil function and host defense against Staphylococcus aureus infection",
      "volume": "98",
      "author": "Caver",
      "year": "1996",
      "journal-title": "J. Clin. Invest."
    },
    {
      "key": "2023072509092903700_R28",
      "doi-asserted-by": "crossref",
      "first-page": "408",
      "DOI": "10.1016/S0960-9822(06)00188-6",
      "article-title": "CD45 regulates Src family member kinase activity associated with macrophage integrin-mediated adhesion",
      "volume": "7",
      "author": "Roach",
      "year": "1997",
      "journal-title": "Curr. Biol."
    },
    {
      "key": "2023072509092903700_R29",
      "doi-asserted-by": "crossref",
      "first-page": "1249",
      "DOI": "10.1083/jcb.135.5.1249",
      "article-title": "A role for phosphoinoside 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages",
      "volume": "135",
      "author": "Araki",
      "year": "1996",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072509092903700_R30",
      "doi-asserted-by": "crossref",
      "first-page": "20332",
      "DOI": "10.1074/jbc.272.33.20332",
      "article-title": "The actin cytoskeleton is required for receptor-mediated endocytosis in mammalian cells",
      "volume": "272",
      "author": "Lamaze",
      "year": "1997",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072509092903700_R31",
      "first-page": "757",
      "article-title": "Ca2+-independent F-actin assembly and disassembly during Fc receptor\u2013mediated phagocytosis in mouse macrophages",
      "volume": "113",
      "author": "Greenberg",
      "year": "1991",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509092903700_R32",
      "doi-asserted-by": "crossref",
      "first-page": "1853",
      "DOI": "10.1084/jem.172.6.1853",
      "article-title": "Colocalization of F-actin and talin during Fc receptor\u2013mediated phagocytosis in mouse macrophages",
      "volume": "172",
      "author": "Greenberg",
      "year": "1990",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509092903700_R33",
      "doi-asserted-by": "crossref",
      "first-page": "627",
      "DOI": "10.1084/jem.184.2.627",
      "article-title": "Molecular definition of distinct cytoskeletal structures involved in complement- and Fc receptor-mediated phagocytosis in macrophages",
      "volume": "184",
      "author": "Allen",
      "year": "1996",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509092903700_R34",
      "doi-asserted-by": "crossref",
      "first-page": "1027",
      "DOI": "10.1084/jem.186.7.1027",
      "article-title": "A critical role for syk in signal transduction and phagocytosis mediated by Fc\u03b3 receptors on macrophages",
      "volume": "186",
      "author": "Crowley",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509092903700_R35",
      "doi-asserted-by": "crossref",
      "first-page": "4209",
      "DOI": "10.1128/MCB.18.7.4209",
      "article-title": "The syk protein tyrosine kinase is essential for Fc\u03b3 receptor signaling in macrophages and neutrophils",
      "volume": "18",
      "author": "Kiefer",
      "year": "1998",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2023072509092903700_R36",
      "doi-asserted-by": "crossref",
      "first-page": "424",
      "DOI": "10.1016/S0962-8924(00)89101-1",
      "article-title": "Macropinocytosis",
      "volume": "5",
      "author": "Swanson",
      "year": "1995",
      "journal-title": "Trends Cell Biol."
    },
    {
      "key": "2023072509092903700_R37",
      "doi-asserted-by": "crossref",
      "first-page": "89",
      "DOI": "10.1016/S0962-8924(00)88956-4",
      "article-title": "Phagocytosis by zippers and triggers",
      "volume": "5",
      "author": "Swanson",
      "year": "1995",
      "journal-title": "Trends Cell Biol."
    },
    {
      "key": "2023072509092903700_R38",
      "doi-asserted-by": "crossref",
      "first-page": "955",
      "DOI": "10.1084/jem.186.6.955",
      "article-title": "Rho is required for the initiation of calcium signaling and phagocytosis by Fc\u03b3 receptors in macrophages",
      "volume": "186",
      "author": "Hackam",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509092903700_R39",
      "doi-asserted-by": "crossref",
      "first-page": "3403",
      "DOI": "10.1096/fasebj.6.15.1281458",
      "article-title": "The src family of tyrosine protein kinases in hemopoietic signal transduction",
      "volume": "6",
      "author": "Bolen",
      "year": "1992",
      "journal-title": "FASEB J."
    },
    {
      "key": "2023072509092903700_R40",
      "doi-asserted-by": "crossref",
      "first-page": "229",
      "DOI": "10.1016/0145-2126(95)00161-1",
      "article-title": "The function of src family tyrosine kinases in hematopoietic cells",
      "volume": "20",
      "author": "Xu",
      "year": "1996",
      "journal-title": "Leuk. Res."
    },
    {
      "key": "2023072509092903700_R41",
      "doi-asserted-by": "crossref",
      "first-page": "149",
      "DOI": "10.1016/S0065-2776(08)60019-X",
      "article-title": "Inhibitory pathways triggered by ITIM-containing receptors",
      "volume": "72",
      "author": "Bolland",
      "year": "1999",
      "journal-title": "Adv. Immunol."
    },
    {
      "key": "2023072509092903700_R42",
      "doi-asserted-by": "crossref",
      "first-page": "2535",
      "DOI": "10.1038/sj.onc.1202203",
      "article-title": "The major SHP-1-binding, tyrosine-phosphorylated protein in macrophages is a member of the KIR/LIR family and an SHP-1 substrate",
      "volume": "17",
      "author": "Berg",
      "year": "1998",
      "journal-title": "Oncogene."
    },
    {
      "key": "2023072509092903700_R43",
      "doi-asserted-by": "crossref",
      "first-page": "3838",
      "DOI": "10.1128/MCB.18.7.3838",
      "article-title": "Identification of major binding proteins and substrates for the SH2-containing protein tyrosine phosphatase SHP-1 in macrophages",
      "volume": "18",
      "author": "Timms",
      "year": "1998",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2023072509092903700_R44",
      "doi-asserted-by": "crossref",
      "first-page": "5",
      "DOI": "10.1172/JCI5928",
      "article-title": "Switched at birtha new family for PECAM-1",
      "volume": "103",
      "author": "Newman",
      "year": "1999",
      "journal-title": "J. Clin. Invest."
    },
    {
      "key": "2023072509092903700_R45",
      "doi-asserted-by": "crossref",
      "first-page": "181",
      "DOI": "10.1038/386181a0",
      "article-title": "A family of proteins that inhibit signalling through tyrosine kinase receptors",
      "volume": "386",
      "author": "Kharitonenkov",
      "year": "1997",
      "journal-title": "Nature."
    },
    {
      "key": "2023072509092903700_R46",
      "doi-asserted-by": "crossref",
      "first-page": "265",
      "DOI": "10.1006/excr.1998.4110",
      "article-title": "Size of the IgG-opsonized particles determines macrophage response during internalization",
      "volume": "242",
      "author": "Koval",
      "year": "1998",
      "journal-title": "Exp. Cell Res."
    },
    {
      "key": "2023072509092903700_R47",
      "doi-asserted-by": "crossref",
      "first-page": "1343",
      "DOI": "10.1084/jem.187.8.1343",
      "article-title": "A double-edged kinase Lyna positive and negative regulator for antigen receptor\u2013mediated signals",
      "volume": "187",
      "author": "Nishizumi",
      "year": "1998",
      "journal-title": "J. Exp. Med"
    },
    {
      "key": "2023072509092903700_R48",
      "doi-asserted-by": "crossref",
      "first-page": "69",
      "DOI": "10.1016/S1074-7613(00)80511-7",
      "article-title": "Characterization of the B lymphocyte populations in lyn-deficient mice and the role of lyn in signal initiation and down-regulation",
      "volume": "7",
      "author": "Chan",
      "year": "1997",
      "journal-title": "Immunity."
    },
    {
      "key": "2023072509092903700_R49",
      "doi-asserted-by": "crossref",
      "first-page": "1762",
      "DOI": "10.1182/blood.V91.5.1762",
      "article-title": "Inhibition of Fc\u03b3 receptor-mediated phagocytosis by a nonphagocytic Fc\u03b3 receptor",
      "volume": "91",
      "author": "Hunter",
      "year": "1998",
      "journal-title": "Blood."
    },
    {
      "key": "2023072509092903700_R50",
      "doi-asserted-by": "crossref",
      "first-page": "559",
      "DOI": "10.1074/jbc.274.2.559",
      "article-title": "Integrin-associated protein is a ligand for the P84 neural adhesion molecule",
      "volume": "274",
      "author": "Jiang",
      "year": "1999",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072509092903700_R51",
      "doi-asserted-by": "crossref",
      "first-page": "2785",
      "DOI": "10.1083/jcb.111.6.2785",
      "article-title": "Integrin-associated proteina 50-kD plasma membrane antigen physically and functionally associated with integrins",
      "volume": "111",
      "author": "Brown",
      "year": "1990",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072509092903700_R52",
      "doi-asserted-by": "crossref",
      "first-page": "519",
      "DOI": "10.1046/j.1365-2567.1997.00367.x",
      "article-title": "The role of the Fgr tyrosine kinase in the control of the adhesive properties of U937 monoblastoid cells and their derivatives",
      "volume": "92",
      "author": "Faulkner",
      "year": "1997",
      "journal-title": "Immunology."
    },
    {
      "key": "2023072509092903700_R53",
      "doi-asserted-by": "crossref",
      "first-page": "8783",
      "DOI": "10.1073/pnas.86.22.8783",
      "article-title": "Translocation of the Fgr protein-tyrosine kinase as a consequence of neutrophil activation",
      "volume": "86",
      "author": "Gutkind",
      "year": "1989",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072509092903700_R54",
      "doi-asserted-by": "crossref",
      "first-page": "348",
      "DOI": "10.1016/S0167-4889(97)00034-7",
      "article-title": "Influence of tyrosine phosphorylation on protein interaction with Fc\u03b3RIIA",
      "volume": "1357",
      "author": "Ibarrola",
      "year": "1997",
      "journal-title": "Biochem. Biophys. Acta."
    },
    {
      "key": "2023072509092903700_R55",
      "doi-asserted-by": "crossref",
      "first-page": "1111",
      "DOI": "10.1083/jcb.126.4.1111",
      "article-title": "\u03b22 integrin\u2013dependent protein tyrosine phosphorylation and activation of the Fgr protein tyrosine kinase in human neutrophils",
      "volume": "126",
      "author": "Berton",
      "year": "1994",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072509092903700_R56",
      "doi-asserted-by": "crossref",
      "first-page": "223",
      "DOI": "10.1111/j.1348-0421.1996.tb03338.x",
      "article-title": "Fgr expression restricted to subpopulation of monocyte/macrophage lineage in resting conditions is induced in various hematopoietic cells after activation or transformation",
      "volume": "40",
      "author": "Hatakeyama",
      "year": "1996",
      "journal-title": "Microbiol. Immunol."
    },
    {
      "key": "2023072509092903700_R57",
      "doi-asserted-by": "crossref",
      "first-page": "7580",
      "DOI": "10.1073/pnas.95.13.7580",
      "article-title": "Resistance to endotoxic shock and reduced neutrophil migration in mice deficient for the src-family kinases hck and fgr",
      "volume": "95",
      "author": "Lowell",
      "year": "1998",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072509092903700_R58",
      "doi-asserted-by": "crossref",
      "first-page": "313",
      "DOI": "10.1002/jlb.65.3.313",
      "article-title": "Integrin signal transduction in myeloid leukocytes",
      "volume": "65",
      "author": "Lowell",
      "year": "1999",
      "journal-title": "J. Leukoc. Biol."
    },
    {
      "key": "2023072509092903700_R59",
      "doi-asserted-by": "crossref",
      "first-page": "4391",
      "DOI": "10.1093/emboj/17.15.4391",
      "article-title": "A beta 1 integrin signalling pathway involving src-family kinases, cbl and PI-3 kinase is required for macrophage spreading and migration",
      "volume": "17",
      "author": "Meng",
      "year": "1998",
      "journal-title": "EMBO (Eur. Mol. Biol. Organ.) J."
    }
  ],
  "container-title": "The Journal of Experimental Medicine",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://rupress.org/jem/article-pdf/191/3/515/1697528/99-1521.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://rupress.org/jem/article-pdf/191/3/515/1697528/99-1521.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        7,
        25
      ]
    ],
    "date-time": "2023-07-25T10:22:47Z",
    "timestamp": 1690280567000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://rupress.org/jem/article/191/3/515/54510/Negative-Regulation-of-Phagocytosis-in-Murine"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2000,
        2,
        7
      ]
    ]
  },
  "references-count": 59,
  "journal-issue": {
    "issue": "3",
    "published-print": {
      "date-parts": [
        [
          2000,
          2,
          7
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1084/jem.191.3.515",
  "relation": {},
  "ISSN": [
    "0022-1007",
    "1540-9538"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2000,
        2,
        7
      ]
    ]
  }
}