KEGG   PATHWAY: hsa04666
Entry
hsa04666                    Pathway                                
Name
Fc gamma R-mediated phagocytosis - Homo sapiens (human)
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
hsa04666  Fc gamma R-mediated phagocytosis
hsa04666

Network
nt06180  Pathogenic Escherichia coli
nt06183  Yersinia
  Element
N01090  IGG-FCGR-RAC signaling pathway
Drug
D11275  Rosiptor (USAN/INN)
D11276  Rosiptor acetate (USAN)
D11339  Valziflocept (USAN)
Other DBs
GO: 0006909
Organism
Homo sapiens (human) [GN:hsa]
Gene
10000  AKT3; RAC-gamma serine/threonine-protein kinase isoform 1 [KO:K04456] [EC:2.7.11.1]
100137049  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
10092  ARPC5; actin-related protein 2/3 complex subunit 5 isoform 1 [KO:K05754]
10093  ARPC4; actin-related protein 2/3 complex subunit 4 isoform a [KO:K05755]
10094  ARPC3; actin-related protein 2/3 complex subunit 3 isoform 1 [KO:K05756]
10095  ARPC1B; actin-related protein 2/3 complex subunit 1B [KO:K05757]
10096  ACTR3; actin-related protein 3 isoform 1 [KO:K18584]
10097  ACTR2; actin-related protein 2 isoform b [KO:K17260]
10109  ARPC2; actin-related protein 2/3 complex subunit 2 [KO:K05758]
10163  WASF2; actin-binding protein WASF2 isoform 1 [KO:K05748]
102723407  [KO:K06856]
10451  VAV3; guanine nucleotide exchange factor VAV3 isoform 1 [KO:K05730]
10552  ARPC1A; actin-related protein 2/3 complex subunit 1A isoform 1 [KO:K05757]
1072  CFL1; cofilin-1 [KO:K05765]
1073  CFL2; cofilin-2 isoform 1 [KO:K05765]
10810  WASF3; actin-binding protein WASF3 isoform 1 [KO:K06083]
110117499  P3R3URF-PIK3R3; LOC110117498-PIK3R3 readthrough [KO:K02649]
123745  PLA2G4E; cytosolic phospholipase A2 epsilon isoform 1 [KO:K16342] [EC:3.1.1.4]
1398  CRK; adapter molecule crk isoform a [KO:K04438]
1399  CRKL; crk-like protein [KO:K04438]
1785  DNM2; dynamin-2 isoform 1 [KO:K23484]
1793  DOCK1; dedicator of cytokinesis protein 1 isoform 2 [KO:K13708]
207  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
208  AKT2; RAC-beta serine/threonine-protein kinase isoform 1 [KO:K04456] [EC:2.7.11.1]
2209  FCGR1A; high affinity immunoglobulin gamma Fc receptor I isoform 2 precursor [KO:K06498]
2212  FCGR2A; low affinity immunoglobulin gamma Fc region receptor II-a isoform 1 precursor [KO:K06472]
2213  FCGR2B; low affinity immunoglobulin gamma Fc region receptor II-b isoform 1 precursor [KO:K12560]
2214  FCGR3A; low affinity immunoglobulin gamma Fc region receptor III-A isoform c precursor [KO:K06463]
2215  FCGR3B; low affinity immunoglobulin gamma Fc region receptor III-B isoform 2 precursor [KO:K06463]
23396  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform 2 [KO:K00889] [EC:2.7.1.68]
255189  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
27040  LAT; linker for activation of T-cells family member 1 isoform a [KO:K07362]
273  AMPH; amphiphysin isoform 1 [KO:K12562]
274  BIN1; myc box-dependent-interacting protein 1 isoform 1 [KO:K12562]
283748  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
2934  GSN; gelsolin isoform a precursor [KO:K05768]
3055  HCK; tyrosine-protein kinase HCK isoform a [KO:K08893] [EC:2.7.10.2]
3635  INPP5D; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 isoform a [KO:K03084] [EC:3.1.3.86]
3636  INPPL1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform 2 [KO:K15909] [EC:3.1.3.86]
382  ARF6; ADP-ribosylation factor 6 [KO:K07941]
3984  LIMK1; LIM domain kinase 1 isoform 1 [KO:K05743] [EC:2.7.11.1]
3985  LIMK2; LIM domain kinase 2 isoform 2a [KO:K05744] [EC:2.7.11.1]
4067  LYN; tyrosine-protein kinase Lyn isoform A [KO:K05854] [EC:2.7.10.2]
4082  MARCKS; myristoylated alanine-rich C-kinase substrate [KO:K12561]
4651  MYO10; unconventional myosin-X [KO:K12559]
5058  PAK1; serine/threonine-protein kinase PAK 1 isoform 2 [KO:K04409] [EC:2.7.11.1]
50807  ASAP1; arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 isoform 1 [KO:K12488]
5290  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform 1 [KO:K00922] [EC:2.7.1.153]
5295  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform 1 [KO:K02649]
5296  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
5321  PLA2G4A; cytosolic phospholipase A2 isoform 1 [KO:K16342] [EC:3.1.1.4]
5335  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform b [KO:K01116] [EC:3.1.4.11]
5336  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
5337  PLD1; phospholipase D1 isoform a [KO:K01115] [EC:3.1.4.4]
5338  PLD2; phospholipase D2 isoform PLD2A [KO:K01115] [EC:3.1.4.4]
55616  ASAP3; arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3 isoform a [KO:K12488]
5578  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
5579  PRKCB; protein kinase C beta type isoform 1 [KO:K19662] [EC:2.7.11.13]
5580  PRKCD; protein kinase C delta type isoform c [KO:K06068] [EC:2.7.11.13]
5581  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
5582  PRKCG; protein kinase C gamma type isoform 2 [KO:K19663] [EC:2.7.11.13]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 isoform 1 [KO:K04371] [EC:2.7.11.24]
5604  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform 1 [KO:K04368] [EC:2.7.12.2]
56848  SPHK2; sphingosine kinase 2 isoform a [KO:K04718] [EC:2.7.1.91]
57180  ACTR3B; actin-related protein 3B isoform 1 [KO:K18584]
5788  PTPRC; receptor-type tyrosine-protein phosphatase C isoform 1 precursor [KO:K06478] [EC:3.1.3.48]
5879  RAC1; ras-related C3 botulinum toxin substrate 1 isoform Rac1 [KO:K04392]
5880  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
5894  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform b [KO:K04366] [EC:2.7.11.1]
6198  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform a [KO:K04688] [EC:2.7.11.1]
6199  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
65108  MARCKSL1; MARCKS-related protein [KO:K13536]
653361  NCF1; neutrophil cytosol factor 1 [KO:K08011]
653857  ACTR3C; actin-related protein 3C isoform a precursor [KO:K18584]
6850  SYK; tyrosine-protein kinase SYK isoform Syk(L) [KO:K05855] [EC:2.7.10.2]
7408  VASP; vasodilator-stimulated phosphoprotein [KO:K06274]
7409  VAV1; proto-oncogene vav isoform 1 [KO:K05730]
7410  VAV2; guanine nucleotide exchange factor VAV2 isoform 1 [KO:K05730]
7454  WAS; actin nucleation-promoting factor WAS isoform 1 [KO:K05747]
81873  ARPC5L; actin-related protein 2/3 complex subunit 5-like protein [KO:K05754]
8394  PIP5K1A; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha isoform 1 [KO:K00889] [EC:2.7.1.68]
8395  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta isoform 2 [KO:K00889] [EC:2.7.1.68]
8398  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform a [KO:K16343] [EC:3.1.1.4]
8503  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform 1 [KO:K02649]
85477  SCIN; scinderin isoform 1 [KO:K05768]
8605  PLA2G4C; cytosolic phospholipase A2 gamma isoform 1 precursor [KO:K16342] [EC:3.1.1.4]
8611  PLPP1; phospholipid phosphatase 1 isoform 1 [KO:K01080] [EC:3.1.3.4]
8612  PLPP2; phospholipid phosphatase 2 isoform 1 [KO:K01080] [EC:3.1.3.4]
8613  PLPP3; phospholipid phosphatase 3 [KO:K01080] [EC:3.1.3.4]
8681  JMJD7-PLA2G4B; JMJD7-PLA2G4B protein isoform b [KO:K16342] [EC:3.1.1.4]
8853  ASAP2; arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 isoform a [KO:K12488]
8877  SPHK1; sphingosine kinase 1 isoform 3 [KO:K04718] [EC:2.7.1.91]
8936  WASF1; actin-binding protein WASF1 [KO:K05753]
9846  GAB2; GRB2-associated-binding protein 2 isoform a [KO:K08091]
998  CDC42; cell division control protein 42 homolog isoform 1 precursor [KO:K04393]
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
PMID:12488490
  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
PMID:11708889
  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
PMID:15466916
  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
PMID:11244038
  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
PMID:18322649
  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
PMID:10376013
  Authors
Kwiatkowska K, Sobota A
  Title
Signaling pathways in phagocytosis.
  Journal
Bioessays 21:422-31 (1999)
DOI:10.1002/(SICI)1521-1878(199905)21:5<422::AID-BIES9>3.0.CO;2-#
Reference
PMID:10577498
  Authors
Greenberg S
  Title
Modular components of phagocytosis.
  Journal
J Leukoc Biol 66:712-7 (1999)
DOI:10.1002/jlb.66.5.712
Reference
PMID:10224668
  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
PMID:11228151
  Authors
May RC, Machesky LM
  Title
Phagocytosis and the actin cytoskeleton.
  Journal
J Cell Sci 114:1061-77 (2001)
Reference
PMID:17050193
  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
PMID:17308335
  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
PMID:11304556
  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
PMID:15485887
  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
PMID:12821647
  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
PMID:10601359
  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
PMID:10755615
  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
PMID:10586078
  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
hsa04020  Calcium signaling pathway
hsa04142  Lysosome biogenesis
hsa04144  Endocytosis
hsa04810  Regulation of actin cytoskeleton
KO pathway
ko04666   

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