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KEGG   PATHWAY: hsa04666
hsa04666                    Pathway                                
Fc gamma R-mediated phagocytosis - Homo sapiens (human)
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.
Organismal Systems; Immune system
Pathway map
hsa04666  Fc gamma R-mediated phagocytosis

nt06180  Pathogenic Escherichia coli
nt06183  Yersinia
N01090  IGG-FCGR-RAC signaling pathway
D11275  Rosiptor (USAN/INN)
D11276  Rosiptor acetate (USAN)
D11339  Valziflocept (USAN)
Other DBs
GO: 0006909
Homo sapiens (human) [GN:hsa]
102723407  IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]
2209  FCGR1A; Fc gamma receptor Ia [KO:K06498]
2212  FCGR2A; Fc gamma receptor IIa [KO:K06472]
2214  FCGR3A; Fc gamma receptor IIIa [KO:K06463]
2215  FCGR3B; Fc gamma receptor IIIb [KO:K06463]
5788  PTPRC; protein tyrosine phosphatase receptor type C [KO:K06478] [EC:]
3055  HCK; HCK proto-oncogene, Src family tyrosine kinase [KO:K08893] [EC:]
4067  LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:]
6850  SYK; spleen associated tyrosine kinase [KO:K05855] [EC:]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:]
6198  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:]
6199  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:]
5335  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:]
5336  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:]
5580  PRKCD; protein kinase C delta [KO:K06068] [EC:]
5581  PRKCE; protein kinase C epsilon [KO:K18050] [EC:]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
123745  PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:]
5321  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:]
8681  JMJD7-PLA2G4B; JMJD7-PLA2G4B readthrough [KO:K16342] [EC:]
100137049  PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:]
8605  PLA2G4C; phospholipase A2 group IVC [KO:K16342] [EC:]
283748  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:]
255189  PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:]
8398  PLA2G6; phospholipase A2 group VI [KO:K16343] [EC:]
4082  MARCKS; myristoylated alanine rich protein kinase C substrate [KO:K12561]
65108  MARCKSL1; MARCKS like 1 [KO:K13536]
5337  PLD1; phospholipase D1 [KO:K01115] [EC:]
5338  PLD2; phospholipase D2 [KO:K01115] [EC:]
8611  PLPP1; phospholipid phosphatase 1 [KO:K01080] [EC:]
8613  PLPP3; phospholipid phosphatase 3 [KO:K01080] [EC:]
8612  PLPP2; phospholipid phosphatase 2 [KO:K01080] [EC:]
8877  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:]
56848  SPHK2; sphingosine kinase 2 [KO:K04718] [EC:]
5578  PRKCA; protein kinase C alpha [KO:K02677] [EC:]
5579  PRKCB; protein kinase C beta [KO:K19662] [EC:]
5582  PRKCG; protein kinase C gamma [KO:K19663] [EC:]
653361  NCF1; neutrophil cytosolic factor 1 [KO:K08011]
2934  GSN; gelsolin [KO:K05768]
85477  SCIN; scinderin [KO:K05768]
10451  VAV3; vav guanine nucleotide exchange factor 3 [KO:K05730]
7409  VAV1; vav guanine nucleotide exchange factor 1 [KO:K05730]
7410  VAV2; vav guanine nucleotide exchange factor 2 [KO:K05730]
998  CDC42; cell division cycle 42 [KO:K04393]
7454  WAS; WASP actin nucleation promoting factor [KO:K05747]
7408  VASP; vasodilator stimulated phosphoprotein [KO:K06274]
10097  ACTR2; actin related protein 2 [KO:K17260]
57180  ACTR3B; actin related protein 3B [KO:K18584]
653857  ACTR3C; actin related protein 3C [KO:K18584]
10096  ACTR3; actin related protein 3 [KO:K18584]
10095  ARPC1B; actin related protein 2/3 complex subunit 1B [KO:K05757]
10552  ARPC1A; actin related protein 2/3 complex subunit 1A [KO:K05757]
10109  ARPC2; actin related protein 2/3 complex subunit 2 [KO:K05758]
10094  ARPC3; actin related protein 2/3 complex subunit 3 [KO:K05756]
10093  ARPC4; actin related protein 2/3 complex subunit 4 [KO:K05755]
10092  ARPC5; actin related protein 2/3 complex subunit 5 [KO:K05754]
81873  ARPC5L; actin related protein 2/3 complex subunit 5 like [KO:K05754]
5879  RAC1; Rac family small GTPase 1 [KO:K04392]
5880  RAC2; Rac family small GTPase 2 [KO:K07860]
8936  WASF1; WASP family member 1 [KO:K05753]
10163  WASF2; WASP family member 2 [KO:K05748]
10810  WASF3; WASP family member 3 [KO:K06083]
5058  PAK1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:]
3984  LIMK1; LIM domain kinase 1 [KO:K05743] [EC:]
3985  LIMK2; LIM domain kinase 2 [KO:K05744] [EC:]
1072  CFL1; cofilin 1 [KO:K05765]
1073  CFL2; cofilin 2 [KO:K05765]
23396  PIP5K1C; phosphatidylinositol-4-phosphate 5-kinase type 1 gamma [KO:K00889] [EC:]
8394  PIP5K1A; phosphatidylinositol-4-phosphate 5-kinase type 1 alpha [KO:K00889] [EC:]
8395  PIP5K1B; phosphatidylinositol-4-phosphate 5-kinase type 1 beta [KO:K00889] [EC:]
382  ARF6; ADP ribosylation factor 6 [KO:K07941]
1398  CRK; CRK proto-oncogene, adaptor protein [KO:K04438]
1399  CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438]
1793  DOCK1; dedicator of cytokinesis 1 [KO:K13708]
50807  ASAP1; ArfGAP with SH3 domain, ankyrin repeat and PH domain 1 [KO:K12488]
55616  ASAP3; ArfGAP with SH3 domain, ankyrin repeat and PH domain 3 [KO:K12488]
8853  ASAP2; ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 [KO:K12488]
2213  FCGR2B; Fc gamma receptor IIb [KO:K12560]
3635  INPP5D; inositol polyphosphate-5-phosphatase D [KO:K03084] [EC:]
3636  INPPL1; inositol polyphosphate phosphatase like 1 [KO:K15909] [EC:]
9846  GAB2; GRB2 associated binding protein 2 [KO:K08091]
27040  LAT; linker for activation of T cells [KO:K07362]
1785  DNM2; dynamin 2 [KO:K23484] [EC:]
273  AMPH; amphiphysin [KO:K12562]
274  BIN1; bridging integrator 1 [KO:K12562]
4651  MYO10; myosin X [KO:K12559]
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
Garcia-Garcia E, Rosales C
Signal transduction during Fc receptor-mediated phagocytosis.
J Leukoc Biol 72:1092-108 (2002)
Cox D, Greenberg S
Phagocytic signaling strategies: Fc(gamma)receptor-mediated phagocytosis as a model system.
Semin Immunol 13:339-45 (2001)
Swanson JA, Hoppe AD
The coordination of signaling during Fc receptor-mediated phagocytosis.
J Leukoc Biol 76:1093-103 (2004)
Ravetch JV, Bolland S
IgG Fc receptors.
Annu Rev Immunol 19:275-90 (2001)
Groves E, Dart AE, Covarelli V, Caron E
Molecular mechanisms of phagocytic uptake in mammalian cells.
Cell Mol Life Sci 65:1957-76 (2008)
Kwiatkowska K, Sobota A
Signaling pathways in phagocytosis.
Greenberg S
Modular components of phagocytosis.
J Leukoc Biol 66:712-7 (1999)
Lennartz MR
Phospholipases and phagocytosis: the role of phospholipid-derived second messengers in phagocytosis.
Int J Biochem Cell Biol 31:415-30 (1999)
May RC, Machesky LM
Phagocytosis and the actin cytoskeleton.
J Cell Sci 114:1061-77 (2001)
Joshi T, Butchar JP, Tridandapani S
Fcgamma receptor signaling in phagocytes.
Int J Hematol 84:210-6 (2006)
Lee WL, Cosio G, Ireton K, Grinstein S
Role of CrkII in Fcgamma receptor-mediated phagocytosis.
J Biol Chem 282:11135-43 (2007)
Uchida H, Kondo A, Yoshimura Y, Mazaki Y, Sabe H
PAG3/Papalpha/KIAA0400, a GTPase-activating protein for ADP-ribosylation factor (ARF), regulates ARF6 in Fcgamma receptor-mediated phagocytosis of macrophages.
J Exp Med 193:955-66 (2001)
Ganesan LP, Wei G, Pengal RA, Moldovan L, Moldovan N, Ostrowski MC, Tridandapani S
The serine/threonine kinase Akt Promotes Fc gamma receptor-mediated phagocytosis in murine macrophages through the activation of p70S6 kinase.
J Biol Chem 279:54416-25 (2004)
Melendez A, Floto RA, Gillooly DJ, Harnett MM, Allen JM
FcgammaRI coupling to phospholipase D initiates sphingosine kinase-mediated calcium mobilization and vesicular trafficking.
J Biol Chem 273:9393-402 (1998)
Gu H, Botelho RJ, Yu M, Grinstein S, Neel BG
Critical role for scaffolding adapter Gab2 in Fc gamma R-mediated phagocytosis.
J Cell Biol 161:1151-61 (2003)
Dana R, Leto TL, Malech HL, Levy R
Essential requirement of cytosolic phospholipase A2 for activation of the phagocyte NADPH oxidase.
J Biol Chem 273:441-5 (1998)
Gold ES, Underhill DM, Morrissette NS, Guo J, McNiven MA, Aderem A
Dynamin 2 is required for phagocytosis in macrophages.
J Exp Med 190:1849-56 (1999)
Gold ES, Morrissette NS, Underhill DM, Guo J, Bassetti M, Aderem A
Amphiphysin IIm, a novel amphiphysin II isoform, is required for macrophage phagocytosis.
Immunity 12:285-92 (2000)
Raeder EM, Mansfield PJ, Hinkovska-Galcheva V, Shayman JA, Boxer LA
Syk activation initiates downstream signaling events during human polymorphonuclear leukocyte phagocytosis.
J Immunol 163:6785-93 (1999)
Sanchez-Mejorada G, Rosales C
Signal transduction by immunoglobulin Fc receptors.
J Leukoc Biol 63:521-33 (1998)
Rosales C (ed).
Molecular Mechanisms of Phagocytosis
Springer (2005)
hsa04020  Calcium signaling pathway
hsa04142  Lysosome
hsa04144  Endocytosis
hsa04810  Regulation of actin cytoskeleton
KO pathway

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