KEGG   PATHWAY: mmu04666
Entry
mmu04666                    Pathway                                

Name
Fc gamma R-mediated phagocytosis - Mus musculus (mouse)
Description
Phagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes take part in this process in higher organisms. After opsonization with antibodies (IgG), foreign extracellular materials are recognized by Fc gamma receptors. Cross-linking of Fc gamma receptors initiates a variety of signals mediated by tyrosine phosphorylation of multiple proteins, which lead through the actin cytoskeleton rearrangements and membrane remodeling to the formation of phagosomes. Nascent phagosomes undergo a process of maturation that involves fusion with lysosomes. The acquisition of lysosomal proteases and release of reactive oxygen species are crucial for digestion of engulfed materials in phagosomes.
Class
Organismal Systems; Immune system
Pathway map
mmu04666  Fc gamma R-mediated phagocytosis
mmu04666

Other DBs
GO: 0006909
Organism
Mus musculus (mouse) [GN:mmu]
Gene
14129  Fcgr1; Fc receptor, IgG, high affinity I [KO:K06498]
246256  Fcgr4; Fc receptor, IgG, low affinity IV [KO:K06463]
19264  Ptprc; protein tyrosine phosphatase, receptor type, C [KO:K06478] [EC:3.1.3.48]
15162  Hck; hemopoietic cell kinase [KO:K08893] [EC:2.7.10.2]
17096  Lyn; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
20963  Syk; spleen tyrosine kinase [KO:K05855] [EC:2.7.10.2]
18706  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
18707  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
74769  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
18709  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
18708  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
18710  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
11651  Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]
11652  Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]
23797  Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]
58988  Rps6kb2; ribosomal protein S6 kinase, polypeptide 2 [KO:K04688] [EC:2.7.11.1]
72508  Rps6kb1; ribosomal protein S6 kinase, polypeptide 1 [KO:K04688] [EC:2.7.11.1]
18803  Plcg1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
234779  Plcg2; phospholipase C, gamma 2 [KO:K05859] [EC:3.1.4.11]
18753  Prkcd; protein kinase C, delta [KO:K06068] [EC:2.7.11.13]
18754  Prkce; protein kinase C, epsilon [KO:K18050] [EC:2.7.11.13]
110157  Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
26395  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26413  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
329502  Pla2g4e; phospholipase A2, group IVE [KO:K16342] [EC:3.1.1.4]
18783  Pla2g4a; phospholipase A2, group IVA (cytosolic, calcium-dependent) [KO:K16342] [EC:3.1.1.4]
211429  Pla2g4b; phospholipase A2, group IVB (cytosolic) [KO:K16342] [EC:3.1.1.4]
232889  Pla2g4c; phospholipase A2, group IVC (cytosolic, calcium-independent) [KO:K16342] [EC:3.1.1.4]
78390  Pla2g4d; phospholipase A2, group IVD [KO:K16342] [EC:3.1.1.4]
271844  Pla2g4f; phospholipase A2, group IVF [KO:K16342] [EC:3.1.1.4]
53357  Pla2g6; phospholipase A2, group VI [KO:K16343] [EC:3.1.1.4]
17118  Marcks; myristoylated alanine rich protein kinase C substrate [KO:K12561]
17357  Marcksl1; MARCKS-like 1 [KO:K13536]
18806  Pld2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
18805  Pld1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
19012  Plpp1; phospholipid phosphatase 1 [KO:K01080] [EC:3.1.3.4]
50784  Plpp2; phospholipid phosphatase 2 [KO:K01080] [EC:3.1.3.4]
67916  Plpp3; phospholipid phosphatase 3 [KO:K01080] [EC:3.1.3.4]
56632  Sphk2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
20698  Sphk1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
18750  Prkca; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
18751  Prkcb; protein kinase C, beta [KO:K19662] [EC:2.7.11.13]
18752  Prkcg; protein kinase C, gamma [KO:K19663] [EC:2.7.11.13]
17969  Ncf1; neutrophil cytosolic factor 1 [KO:K08011]
227753  Gsn; gelsolin [KO:K05768]
20259  Scin; scinderin [KO:K05768]
22324  Vav1; vav 1 oncogene [KO:K05730]
22325  Vav2; vav 2 oncogene [KO:K05730]
57257  Vav3; vav 3 oncogene [KO:K05730]
12540  Cdc42; cell division cycle 42 [KO:K04393]
22376  Was; Wiskott-Aldrich syndrome [KO:K05747]
22323  Vasp; vasodilator-stimulated phosphoprotein [KO:K06274]
66713  Actr2; ARP2 actin-related protein 2 [KO:K17260]
242894  Actr3b; ARP3 actin-related protein 3B [KO:K18584]
74117  Actr3; ARP3 actin-related protein 3 [KO:K18584]
11867  Arpc1b; actin related protein 2/3 complex, subunit 1B [KO:K05757]
56443  Arpc1a; actin related protein 2/3 complex, subunit 1A [KO:K05757]
76709  Arpc2; actin related protein 2/3 complex, subunit 2 [KO:K05758]
56378  Arpc3; actin related protein 2/3 complex, subunit 3 [KO:K05756]
68089  Arpc4; actin related protein 2/3 complex, subunit 4 [KO:K05755]
67771  Arpc5; actin related protein 2/3 complex, subunit 5 [KO:K05754]
74192  Arpc5l; actin related protein 2/3 complex, subunit 5-like [KO:K05754]
19353  Rac1; Rac family small GTPase 1 [KO:K04392]
19354  Rac2; Rac family small GTPase 2 [KO:K07860]
83767  Wasf1; WASP family, member 1 [KO:K05753]
242687  Wasf2; WASP family, member 2 [KO:K05748]
245880  Wasf3; WASP family, member 3 [KO:K06083]
18479  Pak1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
16885  Limk1; LIM-domain containing, protein kinase [KO:K05743] [EC:2.7.11.1]
16886  Limk2; LIM motif-containing protein kinase 2 [KO:K05744] [EC:2.7.11.1]
12631  Cfl1; cofilin 1, non-muscle [KO:K05765]
12632  Cfl2; cofilin 2, muscle [KO:K05765]
18717  Pip5k1c; phosphatidylinositol-4-phosphate 5-kinase, type 1 gamma [KO:K00889] [EC:2.7.1.68]
18719  Pip5k1b; phosphatidylinositol-4-phosphate 5-kinase, type 1 beta [KO:K00889] [EC:2.7.1.68]
18720  Pip5k1a; phosphatidylinositol-4-phosphate 5-kinase, type 1 alpha [KO:K00889] [EC:2.7.1.68]
11845  Arf6; ADP-ribosylation factor 6 [KO:K07941]
12928  Crk; v-crk avian sarcoma virus CT10 oncogene homolog [KO:K04438]
12929  Crkl; v-crk avian sarcoma virus CT10 oncogene homolog-like [KO:K04438]
330662  Dock1; dedicator of cytokinesis 1 [KO:K13708]
230837  Asap3; ArfGAP with SH3 domain, ankyrin repeat and PH domain 3 [KO:K12488]
211914  Asap2; ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 [KO:K12488]
13196  Asap1; ArfGAP with SH3 domain, ankyrin repeat and PH domain1 [KO:K12488]
14130  Fcgr2b; Fc receptor, IgG, low affinity IIb [KO:K12560]
16331  Inpp5d; inositol polyphosphate-5-phosphatase D [KO:K03084] [EC:3.1.3.86]
16332  Inppl1; inositol polyphosphate phosphatase-like 1 [KO:K15909] [EC:3.1.3.86]
14389  Gab2; growth factor receptor bound protein 2-associated protein 2 [KO:K08091]
16797  Lat; linker for activation of T cells [KO:K07362]
13430  Dnm2; dynamin 2 [KO:K23484] [EC:3.6.5.5]
218038  Amph; amphiphysin [KO:K12562]
30948  Bin1; bridging integrator 1 [KO:K12562]
17909  Myo10; myosin X [KO:K12559]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00219  Arachidonate
C00416  Phosphatidate
C01245  D-myo-Inositol 1,4,5-trisphosphate
C04637  1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C06124  Sphingosine 1-phosphate
Reference
  Authors
Garcia-Garcia E, Rosales C
  Title
Signal transduction during Fc receptor-mediated phagocytosis.
  Journal
J Leukoc Biol 72:1092-108 (2002)
DOI:10.1189/jlb.72.6.1092
Reference
  Authors
Cox D, Greenberg S
  Title
Phagocytic signaling strategies: Fc(gamma)receptor-mediated phagocytosis as a model system.
  Journal
Semin Immunol 13:339-45 (2001)
DOI:10.1006/smim.2001.0330
Reference
  Authors
Swanson JA, Hoppe AD
  Title
The coordination of signaling during Fc receptor-mediated phagocytosis.
  Journal
J Leukoc Biol 76:1093-103 (2004)
DOI:10.1189/jlb.0804439
Reference
  Authors
Ravetch JV, Bolland S
  Title
IgG Fc receptors.
  Journal
Annu Rev Immunol 19:275-90 (2001)
DOI:10.1146/annurev.immunol.19.1.275
Reference
  Authors
Groves E, Dart AE, Covarelli V, Caron E
  Title
Molecular mechanisms of phagocytic uptake in mammalian cells.
  Journal
Cell Mol Life Sci 65:1957-76 (2008)
DOI:10.1007/s00018-008-7578-4
Reference
  Authors
Kwiatkowska K, Sobota A
  Title
Signaling pathways in phagocytosis.
  Journal
Reference
  Authors
Greenberg S
  Title
Modular components of phagocytosis.
  Journal
J Leukoc Biol 66:712-7 (1999)
DOI:10.1002/jlb.66.5.712
Reference
  Authors
Lennartz MR
  Title
Phospholipases and phagocytosis: the role of phospholipid-derived second messengers in phagocytosis.
  Journal
Int J Biochem Cell Biol 31:415-30 (1999)
DOI:10.1016/S1357-2725(98)00108-3
Reference
  Authors
May RC, Machesky LM
  Title
Phagocytosis and the actin cytoskeleton.
  Journal
J Cell Sci 114:1061-77 (2001)
Reference
  Authors
Joshi T, Butchar JP, Tridandapani S
  Title
Fcgamma receptor signaling in phagocytes.
  Journal
Int J Hematol 84:210-6 (2006)
DOI:10.1532/IJH97.06140
Reference
  Authors
Lee WL, Cosio G, Ireton K, Grinstein S
  Title
Role of CrkII in Fcgamma receptor-mediated phagocytosis.
  Journal
J Biol Chem 282:11135-43 (2007)
DOI:10.1074/jbc.M700823200
Reference
  Authors
Uchida H, Kondo A, Yoshimura Y, Mazaki Y, Sabe H
  Title
PAG3/Papalpha/KIAA0400, a GTPase-activating protein for ADP-ribosylation factor (ARF), regulates ARF6 in Fcgamma receptor-mediated phagocytosis of macrophages.
  Journal
J Exp Med 193:955-66 (2001)
DOI:10.1084/jem.193.8.955
Reference
  Authors
Ganesan LP, Wei G, Pengal RA, Moldovan L, Moldovan N, Ostrowski MC, Tridandapani S
  Title
The serine/threonine kinase Akt Promotes Fc gamma receptor-mediated phagocytosis in murine macrophages through the activation of p70S6 kinase.
  Journal
J Biol Chem 279:54416-25 (2004)
DOI:10.1074/jbc.M408188200
Reference
PMID:9545263
  Authors
Melendez A, Floto RA, Gillooly DJ, Harnett MM, Allen JM
  Title
FcgammaRI coupling to phospholipase D initiates sphingosine kinase-mediated calcium mobilization and vesicular trafficking.
  Journal
J Biol Chem 273:9393-402 (1998)
DOI:10.1074/jbc.273.16.9393
Reference
  Authors
Gu H, Botelho RJ, Yu M, Grinstein S, Neel BG
  Title
Critical role for scaffolding adapter Gab2 in Fc gamma R-mediated phagocytosis.
  Journal
J Cell Biol 161:1151-61 (2003)
DOI:10.1083/jcb.200212158
Reference
PMID:9417101
  Authors
Dana R, Leto TL, Malech HL, Levy R
  Title
Essential requirement of cytosolic phospholipase A2 for activation of the phagocyte NADPH oxidase.
  Journal
J Biol Chem 273:441-5 (1998)
DOI:10.1074/jbc.273.1.441
Reference
  Authors
Gold ES, Underhill DM, Morrissette NS, Guo J, McNiven MA, Aderem A
  Title
Dynamin 2 is required for phagocytosis in macrophages.
  Journal
J Exp Med 190:1849-56 (1999)
DOI:10.1084/jem.190.12.1849
Reference
  Authors
Gold ES, Morrissette NS, Underhill DM, Guo J, Bassetti M, Aderem A
  Title
Amphiphysin IIm, a novel amphiphysin II isoform, is required for macrophage phagocytosis.
  Journal
Immunity 12:285-92 (2000)
DOI:10.1016/S1074-7613(00)80181-8
Reference
  Authors
Raeder EM, Mansfield PJ, Hinkovska-Galcheva V, Shayman JA, Boxer LA
  Title
Syk activation initiates downstream signaling events during human polymorphonuclear leukocyte phagocytosis.
  Journal
J Immunol 163:6785-93 (1999)
Reference
PMID:9581795
  Authors
Sanchez-Mejorada G, Rosales C
  Title
Signal transduction by immunoglobulin Fc receptors.
  Journal
J Leukoc Biol 63:521-33 (1998)
DOI:10.1002/jlb.63.5.521
Reference
  Authors
Rosales C (ed).
  Title
Molecular Mechanisms of Phagocytosis
  Journal
Springer (2005)
Related
pathway
mmu04020  Calcium signaling pathway
mmu04142  Lysosome
mmu04144  Endocytosis
mmu04810  Regulation of actin cytoskeleton
KO pathway
ko04666   

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