DOI: 10.1084/jem.191.4.669. Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn

Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn

10.1084/jem.191.4.669

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

Macrophage Fcγ receptors (FcγRs) mediate the uptake and destruction of antibody-coated viruses, bacteria, and parasites. We examined FcγR signaling and phagocytic function in bone marrow–derived macrophages from mutant mice lacking the major Src family kinases expressed in these cells, Hck, Fgr, and Lyn. Many FcγR-induced functional responses and signaling events were diminished or delayed in these macrophages, including immunoglobulin (Ig)G-coated erythrocyte phagocytosis, respiratory burst, actin cup formation, and activation of Syk, phosphatidylinositol 3-kinase, and extracellular signal–regulated kinases 1 and 2. Significant reduction of IgG-dependent phagocytosis was not seen in hck−/−fgr−/− or lyn−/− cells, although the single mutant lyn−/− macrophages did manifest signaling defects. Thus, Src family kinases clearly have roles in two events leading to FcγR-mediated phagocytosis, one involving initiation of actin polymerization and the second involving activation of Syk and subsequent internalization. Since FcγR-mediated phagocytosis did occur at modest levels in a delayed fashion in triple mutant macrophages, these Src family kinases are not absolutely required for uptake of IgG-opsonized particles.

Bibliography

Fitzer-Attas, C. J., Lowry, M., Crowley, M. T., Finn, A. J., Meng, F., DeFranco, A. L., & Lowell, C. A. (2000). FcÎ³ ReceptorâMediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn. The Journal of Experimental Medicine, 191(4), 669â682.

Authors 7

Cheryl J. Fitzer-Attas (first)
Malcolm Lowry (additional)
Mary T. Crowley (additional)
Alexander J. Finn (additional)
Fanying Meng (additional)
Anthony L. DeFranco (additional)
Clifford A. Lowell (additional)

References 50 Referenced 207

10.1146/annurev.immunol.15.1.203 / Annu. Rev. Immunol. / Fc receptor biology by Daeron (1997)
10.1146/annurev.immunol.17.1.593 / Annu. Rev. Immunol. / Mechanisms of phagocytosis in macrophages by Aderem (1999)
10.1073/pnas.95.2.652 / Proc. Natl. Acad. Sci. USA. / Fc receptors are required in passive and active immunity to melanoma by Clynes (1998)
10.1016/S0167-5699(97)01007-4 / Immunol. Today. / Clinical significance of IgG Fc receptors and FcγR-directed immunotherapies by Deo (1997)
10.1016/S0014-5793(96)01359-2 / FEBS Lett. / Tyrosine phosphorylation and Fcγ receptor-mediated phagocytosis by Strzelecka (1997)
10.1016/0955-0674(95)80024-7 / Curr. Opin. Cell Biol. / Transmembrane signaling by antigen receptors of B and T lymphocytes by DeFranco (1995)
10.1002/jlb.60.4.433 / J. Leukoc. Biol. / Protein tyrosine phosphorylation in leukocyte activation through receptors for IgG by Santana (1996)
10.1016/S0021-9258(17)37050-3 / J. Biol. Chem. / Physical and functional association of Src-related protein tyrosine kinases with FcγRII in monocytic THP-1 cells by Ghazizadeh (1994)
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 by Hamada (1993)
10.1084/jem.180.3.1165 / J. Exp. Med. / Physical and functional association of the high affinity immunoglobulin G receptor (FcγRI) with the kinases Hck and Lyn by Wang (1994)
10.1146/annurev.immunol.15.1.371 / Annu. Rev. Immunol. / Leukocyte protein tyrosine kinasespotential targets for drug discovery by Bolen (1997)
10.1182/blood.V85.5.1175.bloodjournal8551175 / Blood. / Induction of phagocytosis by a protein tyrosine kinase by Indik (1995)
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)
10.1083/jcb.135.5.1249 / J. Cell Biol. / A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages by Araki (1996)
10.1074/jbc.271.11.6458 / J. Biol. Chem. / Reconstitution of B cell antigen receptor-induced signaling events in a non-lymphoid cell line by expressing the Syk protein tyrosine kinase by Richards (1996)
10.1038/345810a0 / Nature. / Stimulation of protein tyrosine phosphorylation by the B-lymphocyte antigen receptor by Gold (1990)
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/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)
10.1084/jem.185.9.1661 / J. Exp. Med. / Lipopolysaccharide (LPS)-induced macrophage activation and signal transduction in the absence of Src-family kinases Hck, Fgr, and Lyn by Meng (1997)
10.1016/S0076-6879(86)32008-1 / Methods Enzymol. / Methods for distinguishing ingested from adhering particles by Hed (1986)
10.1016/0022-1759(90)90052-W / J. Immunol. Methods. / Measurement of superoxide release in the phagovacuoles of immune complex-stimulated human neutrophils by Ryan (1990)
10.1073/pnas.93.7.2774 / Proc. Natl. Acad. Sci. USA. / Activation of c-Jun N-terminal kinase in bacterial lipopolysaccharide-stimulated macrophages by Hambleton (1996)
10.4049/jimmunol.148.7.2012 / J. Immunol. / Membrane Ig cross-linking regulates phosphatidylinositol 3-kinase in B lymphocytes by Gold (1992)
10.1016/S0171-2985(98)80062-4 / Immunobiology. / A microscopic study of FcγRIII-mediated respiratory burst in neutrophils by Model (1998)
10.1083/jcb.125.6.1407 / J. Cell Biol. / CR3 (Mac-1, αMβ2, CD11b/CD18) and FcγRIII cooperate in generation of a neutrophil respiratory burstrequirement for FcγRIII and tyrosine phosphorylation by Zhou (1994)
10.1002/j.1460-2075.1995.tb07019.x / EMBO (Eur. Mol. Biol. Organ.) J. / Two distinct regions of FcγRI initiate separate signalling pathways involved in endocytosis and phagocytosis by Davis (1995)
10.1084/jem.177.2.529 / J. Exp. Med. / Tyrosine phosphorylation is required for Fc receptor–mediated phagocytosis in mouse macrophages by Greenberg (1993)
10.1016/S0021-9258(17)41945-4 / J. Biol. Chem. / Tyrosine phosphorylation of the γ-subunit of Fcγ receptors, p72syk, and paxillin during Fc receptor-mediated phagocytosis in macrophages by Greenberg (1994)
10.1038/353855a0 / Nature. / Phosphorylation and dephosphorylation of the high-affinity receptor for immunoglobulin E immediately after receptor engagement and disengagement by Paolini (1991)
10.1126/science.271.5255.1533 / Science. / Phosphoinositides as regulators in membrane traffic by De Camilli (1996)
10.1016/S0960-9822(96)00749-X / Curr. Biol. / Phosphatidylinositol 3-kinase signals activate a selective subset of Rac/Rho-dependent effector pathways by Reif (1996)
10.1074/jbc.270.24.14347 / J. Biol. Chem. / Tyrosine phosphorylation and translocation of the c-cbl protein after activation of tyrosine kinase signaling pathways by Tanaka (1995)
10.1016/S0898-6568(97)00179-4 / Cell Signal. / Cblcomplex formation and functional implications by Liu (1998)
10.1016/S0021-9258(17)31707-6 / J. Biol. Chem. / Involvement of phosphatidylinositol 3-kinase in Fcγ receptor signaling by Ninomiya (1994)
10.1016/0014-5793(96)00122-6 / FEBS Lett. / Specific association of phosphatidylinositol 3-kinase with the protooncogene product Cbl in Fcγ receptor signaling by Matsuo (1996)
10.1023/A:1022347808042 / Inflammation. / Mitogen-activated protein kinase is activated during IgG-mediated phagocytosis, but is not required for target ingestion by Karimi (1998)
10.4049/jimmunol.158.7.3433 / J. Immunol. / Fcγ receptor cross-linking activates p42, p38, and JNK/SAPK mitogen-activated protein kinases in murine macrophagesrole for p42MAPK in Fcγ receptor-stimulated TNF-α synthesis by Rose (1997)
10.1084/jem.186.9.1487 / J. Exp. Med. / Requirements for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes by Cox (1997)
10.1016/S0092-8674(05)80018-2 / Cell. / The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway by Coso (1995)
10.1182/blood.V87.5.1780.1780 / Blood. / Deficiency of the Hck and Src tyrosine kinases results in extreme levels of extramedullary hematopoiesis by Lowell (1996)
10.1002/jlb.63.5.521 / J. Leukoc. Biol. / Signal transduction by immunoglobulin Fc receptors by Sanchez-Mejorada (1998)
10.1073/pnas.93.3.1103 / Proc. Natl. Acad. Sci. USA. / Clustered syk tyrosine kinase domains trigger phagocytosis by Greenberg (1996)
10.4049/jimmunol.160.1.145 / J. Immunol. / Harnessing Syk family tyrosine kinases as signaling domains for chimeric single chain of the variable domain receptors. Optimal design for T cell activation by Fitzer-Attas (1998)
10.1128/MCB.15.3.1582 / Mol. Cell. Biol. / Clustering of Syk is sufficient to induce tyrosine phosphorylation and release of allergic mediators from rat basophilic leukemia cells by Rivera (1995)
10.1074/jbc.271.37.22782 / J. Biol. Chem. / Differential intrinsic enzymatic activity of Syk and Zap-70 protein-tyrosine kinases by Latour (1996)
10.4049/jimmunol.158.4.1650 / J. Immunol. / Protein tyrosine kinases Syk and ZAP-70 display distinct requirements for Src family kinases in immune response receptor signal transduction by Zoller (1997)
10.1074/jbc.271.28.16597 / J. Biol. Chem. / Syk tyrosine kinase is required for immunoreceptor tyrosine activation motif-dependent actin assembly by Cox (1996)
10.1128/MCB.16.9.4735 / Mol. Cell. Biol. / In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor (FcγRII) phosphorylation by Bewarder (1996)
10.1002/eji.1830270810 / Eur. J. Immunol. / Src family-selective tyrosine kinase inhibitor, PP1, inhibits both FcεRI- and Thy-1-mediated activation of rat basophilic leukemia cells by Amoui (1997)

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, 6:27 a.m.)
Indexed	3 weeks, 5 days ago (Aug. 2, 2025, 1:26 a.m.)
Issued	25 years, 6 months ago (Feb. 21, 2000)
Published	25 years, 6 months ago (Feb. 21, 2000)
Published Online	25 years, 6 months ago (Feb. 21, 2000)
Published Print	25 years, 6 months ago (Feb. 21, 2000)

Funders 0

None

BibTeX

@article{Fitzer_Attas_2000, title={Fcγ Receptor–Mediated Phagocytosis in Macrophages Lacking the Src Family Tyrosine Kinases Hck, Fgr, and Lyn}, volume={191}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.191.4.669}, DOI={10.1084/jem.191.4.669}, number={4}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Fitzer-Attas, Cheryl J. and Lowry, Malcolm and Crowley, Mary T. and Finn, Alexander J. and Meng, Fanying and DeFranco, Anthony L. and Lowell, Clifford A.}, year={2000}, month=feb, pages={669–682} }

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      "doi-asserted-by": "crossref",
      "first-page": "203",
      "DOI": "10.1146/annurev.immunol.15.1.203",
      "article-title": "Fc receptor biology",
      "volume": "15",
      "author": "Daeron",
      "year": "1997",
      "journal-title": "Annu. Rev. Immunol."
    },
    {
      "key": "2023072509130820400_R2",
      "doi-asserted-by": "crossref",
      "first-page": "593",
      "DOI": "10.1146/annurev.immunol.17.1.593",
      "article-title": "Mechanisms of phagocytosis in macrophages",
      "volume": "17",
      "author": "Aderem",
      "year": "1999",
      "journal-title": "Annu. Rev. Immunol."
    },
    {
      "key": "2023072509130820400_R3",
      "doi-asserted-by": "crossref",
      "first-page": "652",
      "DOI": "10.1073/pnas.95.2.652",
      "article-title": "Fc receptors are required in passive and active immunity to melanoma",
      "volume": "95",
      "author": "Clynes",
      "year": "1998",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072509130820400_R4",
      "doi-asserted-by": "crossref",
      "first-page": "127",
      "DOI": "10.1016/S0167-5699(97)01007-4",
      "article-title": "Clinical significance of IgG Fc receptors and Fc\u03b3R-directed immunotherapies",
      "volume": "18",
      "author": "Deo",
      "year": "1997",
      "journal-title": "Immunol. Today."
    },
    {
      "key": "2023072509130820400_R5",
      "doi-asserted-by": "crossref",
      "first-page": "11",
      "DOI": "10.1016/S0014-5793(96)01359-2",
      "article-title": "Tyrosine phosphorylation and Fc\u03b3 receptor-mediated phagocytosis",
      "volume": "400",
      "author": "Strzelecka",
      "year": "1997",
      "journal-title": "FEBS Lett."
    },
    {
      "key": "2023072509130820400_R6",
      "doi-asserted-by": "crossref",
      "first-page": "163",
      "DOI": "10.1016/0955-0674(95)80024-7",
      "article-title": "Transmembrane signaling by antigen receptors of B and T lymphocytes",
      "volume": "7",
      "author": "DeFranco",
      "year": "1995",
      "journal-title": "Curr. Opin. Cell Biol."
    },
    {
      "key": "2023072509130820400_R7",
      "doi-asserted-by": "crossref",
      "first-page": "433",
      "DOI": "10.1002/jlb.60.4.433",
      "article-title": "Protein tyrosine phosphorylation in leukocyte activation through receptors for IgG",
      "volume": "60",
      "author": "Santana",
      "year": "1996",
      "journal-title": "J. Leukoc. Biol."
    },
    {
      "key": "2023072509130820400_R8",
      "doi-asserted-by": "crossref",
      "first-page": "8878",
      "DOI": "10.1016/S0021-9258(17)37050-3",
      "article-title": "Physical and functional association of Src-related protein tyrosine kinases with Fc\u03b3RII in monocytic THP-1 cells",
      "volume": "269",
      "author": "Ghazizadeh",
      "year": "1994",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072509130820400_R9",
      "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",
      "volume": "90",
      "author": "Hamada",
      "year": "1993",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072509130820400_R10",
      "doi-asserted-by": "crossref",
      "first-page": "1165",
      "DOI": "10.1084/jem.180.3.1165",
      "article-title": "Physical and functional association of the high affinity immunoglobulin G receptor (Fc\u03b3RI) with the kinases Hck and Lyn",
      "volume": "180",
      "author": "Wang",
      "year": "1994",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509130820400_R11",
      "doi-asserted-by": "crossref",
      "first-page": "371",
      "DOI": "10.1146/annurev.immunol.15.1.371",
      "article-title": "Leukocyte protein tyrosine kinasespotential targets for drug discovery",
      "volume": "15",
      "author": "Bolen",
      "year": "1997",
      "journal-title": "Annu. Rev. Immunol."
    },
    {
      "key": "2023072509130820400_R12",
      "doi-asserted-by": "crossref",
      "first-page": "1175",
      "DOI": "10.1182/blood.V85.5.1175.bloodjournal8551175",
      "article-title": "Induction of phagocytosis by a protein tyrosine kinase",
      "volume": "85",
      "author": "Indik",
      "year": "1995",
      "journal-title": "Blood."
    },
    {
      "key": "2023072509130820400_R13",
      "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": "2023072509130820400_R14",
      "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": "2023072509130820400_R15",
      "doi-asserted-by": "crossref",
      "first-page": "1249",
      "DOI": "10.1083/jcb.135.5.1249",
      "article-title": "A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages",
      "volume": "135",
      "author": "Araki",
      "year": "1996",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072509130820400_R16",
      "doi-asserted-by": "crossref",
      "first-page": "6458",
      "DOI": "10.1074/jbc.271.11.6458",
      "article-title": "Reconstitution of B cell antigen receptor-induced signaling events in a non-lymphoid cell line by expressing the Syk protein tyrosine kinase",
      "volume": "271",
      "author": "Richards",
      "year": "1996",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072509130820400_R17",
      "doi-asserted-by": "crossref",
      "first-page": "810",
      "DOI": "10.1038/345810a0",
      "article-title": "Stimulation of protein tyrosine phosphorylation by the B-lymphocyte antigen receptor",
      "volume": "345",
      "author": "Gold",
      "year": "1990",
      "journal-title": "Nature."
    },
    {
      "key": "2023072509130820400_R18",
      "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": "2023072509130820400_R19",
      "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": "2023072509130820400_R20",
      "doi-asserted-by": "crossref",
      "first-page": "1661",
      "DOI": "10.1084/jem.185.9.1661",
      "article-title": "Lipopolysaccharide (LPS)-induced macrophage activation and signal transduction in the absence of Src-family kinases Hck, Fgr, and Lyn",
      "volume": "185",
      "author": "Meng",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509130820400_R21",
      "doi-asserted-by": "crossref",
      "first-page": "198",
      "DOI": "10.1016/S0076-6879(86)32008-1",
      "article-title": "Methods for distinguishing ingested from adhering particles",
      "volume": "132",
      "author": "Hed",
      "year": "1986",
      "journal-title": "Methods Enzymol."
    },
    {
      "key": "2023072509130820400_R22",
      "doi-asserted-by": "crossref",
      "first-page": "223",
      "DOI": "10.1016/0022-1759(90)90052-W",
      "article-title": "Measurement of superoxide release in the phagovacuoles of immune complex-stimulated human neutrophils",
      "volume": "130",
      "author": "Ryan",
      "year": "1990",
      "journal-title": "J. Immunol. Methods."
    },
    {
      "key": "2023072509130820400_R23",
      "doi-asserted-by": "crossref",
      "first-page": "2774",
      "DOI": "10.1073/pnas.93.7.2774",
      "article-title": "Activation of c-Jun N-terminal kinase in bacterial lipopolysaccharide-stimulated macrophages",
      "volume": "93",
      "author": "Hambleton",
      "year": "1996",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072509130820400_R24",
      "doi-asserted-by": "crossref",
      "first-page": "2012",
      "DOI": "10.4049/jimmunol.148.7.2012",
      "article-title": "Membrane Ig cross-linking regulates phosphatidylinositol 3-kinase in B lymphocytes",
      "volume": "148",
      "author": "Gold",
      "year": "1992",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072509130820400_R25",
      "doi-asserted-by": "crossref",
      "first-page": "39",
      "DOI": "10.1016/S0171-2985(98)80062-4",
      "article-title": "A microscopic study of Fc\u03b3RIII-mediated respiratory burst in neutrophils",
      "volume": "199",
      "author": "Model",
      "year": "1998",
      "journal-title": "Immunobiology."
    },
    {
      "key": "2023072509130820400_R26",
      "doi-asserted-by": "crossref",
      "first-page": "1407",
      "DOI": "10.1083/jcb.125.6.1407",
      "article-title": "CR3 (Mac-1, \u03b1M\u03b22, CD11b/CD18) and Fc\u03b3RIII cooperate in generation of a neutrophil respiratory burstrequirement for Fc\u03b3RIII and tyrosine phosphorylation",
      "volume": "125",
      "author": "Zhou",
      "year": "1994",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072509130820400_R27",
      "doi-asserted-by": "crossref",
      "first-page": "432",
      "DOI": "10.1002/j.1460-2075.1995.tb07019.x",
      "article-title": "Two distinct regions of Fc\u03b3RI initiate separate signalling pathways involved in endocytosis and phagocytosis",
      "volume": "14",
      "author": "Davis",
      "year": "1995",
      "journal-title": "EMBO (Eur. Mol. Biol. Organ.) J."
    },
    {
      "key": "2023072509130820400_R28",
      "doi-asserted-by": "crossref",
      "first-page": "529",
      "DOI": "10.1084/jem.177.2.529",
      "article-title": "Tyrosine phosphorylation is required for Fc receptor\u2013mediated phagocytosis in mouse macrophages",
      "volume": "177",
      "author": "Greenberg",
      "year": "1993",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509130820400_R29",
      "doi-asserted-by": "crossref",
      "first-page": "3897",
      "DOI": "10.1016/S0021-9258(17)41945-4",
      "article-title": "Tyrosine phosphorylation of the \u03b3-subunit of Fc\u03b3 receptors, p72syk, and paxillin during Fc receptor-mediated phagocytosis in macrophages",
      "volume": "269",
      "author": "Greenberg",
      "year": "1994",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072509130820400_R30",
      "doi-asserted-by": "crossref",
      "first-page": "855",
      "DOI": "10.1038/353855a0",
      "article-title": "Phosphorylation and dephosphorylation of the high-affinity receptor for immunoglobulin E immediately after receptor engagement and disengagement",
      "volume": "353",
      "author": "Paolini",
      "year": "1991",
      "journal-title": "Nature."
    },
    {
      "key": "2023072509130820400_R31",
      "doi-asserted-by": "crossref",
      "first-page": "1533",
      "DOI": "10.1126/science.271.5255.1533",
      "article-title": "Phosphoinositides as regulators in membrane traffic",
      "volume": "271",
      "author": "De Camilli",
      "year": "1996",
      "journal-title": "Science."
    },
    {
      "key": "2023072509130820400_R32",
      "doi-asserted-by": "crossref",
      "first-page": "1445",
      "DOI": "10.1016/S0960-9822(96)00749-X",
      "article-title": "Phosphatidylinositol 3-kinase signals activate a selective subset of Rac/Rho-dependent effector pathways",
      "volume": "6",
      "author": "Reif",
      "year": "1996",
      "journal-title": "Curr. Biol."
    },
    {
      "key": "2023072509130820400_R33",
      "doi-asserted-by": "crossref",
      "first-page": "14347",
      "DOI": "10.1074/jbc.270.24.14347",
      "article-title": "Tyrosine phosphorylation and translocation of the c-cbl protein after activation of tyrosine kinase signaling pathways",
      "volume": "270",
      "author": "Tanaka",
      "year": "1995",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072509130820400_R34",
      "doi-asserted-by": "crossref",
      "first-page": "377",
      "DOI": "10.1016/S0898-6568(97)00179-4",
      "article-title": "Cblcomplex formation and functional implications",
      "volume": "10",
      "author": "Liu",
      "year": "1998",
      "journal-title": "Cell Signal."
    },
    {
      "key": "2023072509130820400_R35",
      "doi-asserted-by": "crossref",
      "first-page": "22732",
      "DOI": "10.1016/S0021-9258(17)31707-6",
      "article-title": "Involvement of phosphatidylinositol 3-kinase in Fc\u03b3 receptor signaling",
      "volume": "269",
      "author": "Ninomiya",
      "year": "1994",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072509130820400_R36",
      "doi-asserted-by": "crossref",
      "first-page": "11",
      "DOI": "10.1016/0014-5793(96)00122-6",
      "article-title": "Specific association of phosphatidylinositol 3-kinase with the protooncogene product Cbl in Fc\u03b3 receptor signaling",
      "volume": "382",
      "author": "Matsuo",
      "year": "1996",
      "journal-title": "FEBS Lett."
    },
    {
      "key": "2023072509130820400_R37",
      "doi-asserted-by": "crossref",
      "first-page": "67",
      "DOI": "10.1023/A:1022347808042",
      "article-title": "Mitogen-activated protein kinase is activated during IgG-mediated phagocytosis, but is not required for target ingestion",
      "volume": "22",
      "author": "Karimi",
      "year": "1998",
      "journal-title": "Inflammation."
    },
    {
      "key": "2023072509130820400_R38",
      "doi-asserted-by": "crossref",
      "first-page": "3433",
      "DOI": "10.4049/jimmunol.158.7.3433",
      "article-title": "Fc\u03b3 receptor cross-linking activates p42, p38, and JNK/SAPK mitogen-activated protein kinases in murine macrophagesrole for p42MAPK in Fc\u03b3 receptor-stimulated TNF-\u03b1 synthesis",
      "volume": "158",
      "author": "Rose",
      "year": "1997",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072509130820400_R39",
      "doi-asserted-by": "crossref",
      "first-page": "1487",
      "DOI": "10.1084/jem.186.9.1487",
      "article-title": "Requirements for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes",
      "volume": "186",
      "author": "Cox",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072509130820400_R40",
      "doi-asserted-by": "crossref",
      "first-page": "1137",
      "DOI": "10.1016/S0092-8674(05)80018-2",
      "article-title": "The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway",
      "volume": "81",
      "author": "Coso",
      "year": "1995",
      "journal-title": "Cell."
    },
    {
      "key": "2023072509130820400_R41",
      "doi-asserted-by": "crossref",
      "first-page": "1780",
      "DOI": "10.1182/blood.V87.5.1780.1780",
      "article-title": "Deficiency of the Hck and Src tyrosine kinases results in extreme levels of extramedullary hematopoiesis",
      "volume": "87",
      "author": "Lowell",
      "year": "1996",
      "journal-title": "Blood."
    },
    {
      "key": "2023072509130820400_R42",
      "doi-asserted-by": "crossref",
      "first-page": "521",
      "DOI": "10.1002/jlb.63.5.521",
      "article-title": "Signal transduction by immunoglobulin Fc receptors",
      "volume": "63",
      "author": "Sanchez-Mejorada",
      "year": "1998",
      "journal-title": "J. Leukoc. Biol."
    },
    {
      "key": "2023072509130820400_R43",
      "doi-asserted-by": "crossref",
      "first-page": "1103",
      "DOI": "10.1073/pnas.93.3.1103",
      "article-title": "Clustered syk tyrosine kinase domains trigger phagocytosis",
      "volume": "93",
      "author": "Greenberg",
      "year": "1996",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072509130820400_R44",
      "doi-asserted-by": "crossref",
      "first-page": "145",
      "DOI": "10.4049/jimmunol.160.1.145",
      "article-title": "Harnessing Syk family tyrosine kinases as signaling domains for chimeric single chain of the variable domain receptors. Optimal design for T cell activation",
      "volume": "160",
      "author": "Fitzer-Attas",
      "year": "1998",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072509130820400_R45",
      "doi-asserted-by": "crossref",
      "first-page": "1582",
      "DOI": "10.1128/MCB.15.3.1582",
      "article-title": "Clustering of Syk is sufficient to induce tyrosine phosphorylation and release of allergic mediators from rat basophilic leukemia cells",
      "volume": "15",
      "author": "Rivera",
      "year": "1995",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2023072509130820400_R46",
      "doi-asserted-by": "crossref",
      "first-page": "22782",
      "DOI": "10.1074/jbc.271.37.22782",
      "article-title": "Differential intrinsic enzymatic activity of Syk and Zap-70 protein-tyrosine kinases",
      "volume": "271",
      "author": "Latour",
      "year": "1996",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072509130820400_R47",
      "doi-asserted-by": "crossref",
      "first-page": "1650",
      "DOI": "10.4049/jimmunol.158.4.1650",
      "article-title": "Protein tyrosine kinases Syk and ZAP-70 display distinct requirements for Src family kinases in immune response receptor signal transduction",
      "volume": "158",
      "author": "Zoller",
      "year": "1997",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072509130820400_R48",
      "doi-asserted-by": "crossref",
      "first-page": "16597",
      "DOI": "10.1074/jbc.271.28.16597",
      "article-title": "Syk tyrosine kinase is required for immunoreceptor tyrosine activation motif-dependent actin assembly",
      "volume": "271",
      "author": "Cox",
      "year": "1996",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072509130820400_R49",
      "doi-asserted-by": "crossref",
      "first-page": "4735",
      "DOI": "10.1128/MCB.16.9.4735",
      "article-title": "In vivo and in vitro specificity of protein tyrosine kinases for immunoglobulin G receptor (Fc\u03b3RII) phosphorylation",
      "volume": "16",
      "author": "Bewarder",
      "year": "1996",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2023072509130820400_R50",
      "doi-asserted-by": "crossref",
      "first-page": "1881",
      "DOI": "10.1002/eji.1830270810",
      "article-title": "Src family-selective tyrosine kinase inhibitor, PP1, inhibits both Fc\u03b5RI- and Thy-1-mediated activation of rat basophilic leukemia cells",
      "volume": "27",
      "author": "Amoui",
      "year": "1997",
      "journal-title": "Eur. J. Immunol."
    }
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