KEGG   PATHWAY: pcad04666
Entry
pcad04666                   Pathway                                
Name
Fc gamma R-mediated phagocytosis - Physeter macrocephalus (sperm whale)
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
pcad04666  Fc gamma R-mediated phagocytosis
pcad04666

Other DBs
GO: 0006909
Organism
Physeter macrocephalus (sperm whale) [GN:pcad]
Gene
102973503  [KO:K12488]
102973743  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
102973790  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta [KO:K00889] [EC:2.7.1.68]
102974288  MARCKSL1; MARCKS-related protein [KO:K13536]
102974383  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
102974888  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
102975027  PLPP1; phospholipid phosphatase 1 isoform X3 [KO:K01080] [EC:3.1.3.4]
102975555  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102975714  ARPC4; actin-related protein 2/3 complex subunit 4 [KO:K05755]
102975958  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
102976265  WASF2; actin-binding protein WASF2 [KO:K05748]
102976346  VAV1; proto-oncogene vav [KO:K05730]
102976827  SCIN; scinderin isoform X1 [KO:K05768]
102976885  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
102976971  AKT3; RAC-gamma serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
102977108  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102977222  GSN; gelsolin isoform X1 [KO:K05768]
102977689  HCK; tyrosine-protein kinase HCK isoform X1 [KO:K08893] [EC:2.7.10.2]
102977886  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
102977902  [KO:K05765]
102978005  [KO:K04409] [EC:2.7.11.1]
102978208  WASF3; actin-binding protein WASF3 isoform X1 [KO:K06083]
102978946  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
102978952  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102978953  AMPH; amphiphysin [KO:K12562]
102979195  [KO:K04392]
102979871  ASAP2; arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 isoform X1 [KO:K12488]
102980332  WASF1; actin-binding protein WASF1 isoform X3 [KO:K05753]
102981282  [KO:K18584]
102981524  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102981826  DOCK1; dedicator of cytokinesis protein 1 [KO:K13708]
102982090  ASAP3; arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3 [KO:K12488]
102982276  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
102982526  [KO:K12562]
102982542  NCF1; neutrophil cytosol factor 1 isoform X2 [KO:K08011]
102982650  [KO:K05765]
102982912  SPHK1; LOW QUALITY PROTEIN: sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
102983188  PLA2G4D; cytosolic phospholipase A2 delta isoform X1 [KO:K16342] [EC:3.1.1.4]
102983230  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
102983608  ACTR2; actin-related protein 2 isoform X2 [KO:K17260]
102983681  PLA2G4F; LOW QUALITY PROTEIN: cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
102983841  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
102983864  [KO:K12560]
102984031  GAB2; GRB2-associated-binding protein 2 isoform X1 [KO:K08091]
102984239  PLA2G4E; cytosolic phospholipase A2 epsilon isoform X2 [KO:K16342] [EC:3.1.1.4]
102984263  ARPC3; actin-related protein 2/3 complex subunit 3 [KO:K05756]
102984279  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
102984305  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102984528  [KO:K18584]
102984630  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
102985111  PLA2G4A; cytosolic phospholipase A2 isoform X1 [KO:K16342] [EC:3.1.1.4]
102986098  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102986111  LIMK1; LIM domain kinase 1 [KO:K05743] [EC:2.7.11.1]
102986218  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
102986342  [KO:K05757]
102987316  ARPC5; actin-related protein 2/3 complex subunit 5 [KO:K05754]
102987866  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
102988075  PIP5K1A; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha isoform X3 [KO:K00889] [EC:2.7.1.68]
102988564  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
102988604  PTPRC; receptor-type tyrosine-protein phosphatase C [KO:K06478] [EC:3.1.3.48]
102988770  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
102988824  WAS; actin nucleation-promoting factor WAS [KO:K05747]
102989074  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102990087  [KO:K04456] [EC:2.7.11.1]
102990100  CRKL; crk-like protein [KO:K04438]
102990180  LIMK2; LIM domain kinase 2 isoform X1 [KO:K05744] [EC:2.7.11.1]
102990276  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X2 [KO:K04392]
102990399  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
102990552  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
102990690  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
102990877  [KO:K06463]
102991058  MYO10; unconventional myosin-X isoform X1 [KO:K12559]
102991192  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
102991476  DNM2; dynamin-2 [KO:K23484]
102991729  [KO:K01080] [EC:3.1.3.4]
102991779  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102991986  [KO:K05758]
102992191  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102992270  CFL2; cofilin-2 isoform X2 [KO:K05765]
102992700  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
102992923  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
102993186  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
102993697  INPPL1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X1 [KO:K15909] [EC:3.1.3.86]
102994205  PLPP2; LOW QUALITY PROTEIN: phospholipid phosphatase 2 [KO:K01080] [EC:3.1.3.4]
102994214  CRK; adapter molecule crk isoform X1 [KO:K04438]
102994479  [KO:K05758]
102994496  INPP5D; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 [KO:K03084] [EC:3.1.3.86]
102994529  SPHK2; sphingosine kinase 2 isoform X1 [KO:K04718] [EC:2.7.1.91]
102994582  [KO:K05757]
102994897  ACTR3B; actin-related protein 3B isoform X1 [KO:K18584]
102994990  [KO:K01080] [EC:3.1.3.4]
102995014  ARPC5L; actin-related protein 2/3 complex subunit 5-like protein [KO:K05754]
102995811  ARPC1B; actin-related protein 2/3 complex subunit 1B isoform X2 [KO:K05757]
102996647  ARPC1A; actin-related protein 2/3 complex subunit 1A isoform X3 [KO:K05757]
102997003  [KO:K05754]
112062101  MARCKS; myristoylated alanine-rich C-kinase substrate [KO:K12561]
112062432  [KO:K06472]
112065100  ARPC2; LOW QUALITY PROTEIN: actin-related protein 2/3 complex subunit 2 [KO:K05758]
112067148  [KO:K07941]
112067442  [KO:K05765]
114484958  [KO:K23484]
114487309  BIN1; myc box-dependent-interacting protein 1 [KO:K12562]
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
pcad04020  Calcium signaling pathway
pcad04142  Lysosome
pcad04144  Endocytosis
pcad04810  Regulation of actin cytoskeleton
KO pathway
ko04666   

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