KEGG   PATHWAY: ko04666
Entry
ko04666                     Pathway                                
Name
Fc gamma R-mediated phagocytosis
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
ko04666  Fc gamma R-mediated phagocytosis
ko04666

Drug
D05994  Talizumab (USAN/INN)
Other DBs
GO: 0006909
Orthology
K00889  PIP5K; 1-phosphatidylinositol-4-phosphate 5-kinase [EC:2.7.1.68]
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01080  PLPP1_2_3; phosphatidate phosphatase [EC:3.1.3.4]
K01115  PLD1_2; phospholipase D1/2 [EC:3.1.4.4]
K01116  PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02677  PRKCA; classical protein kinase C alpha type [EC:2.7.11.13]
K03084  SHIP1, INPP5D; phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 1 [EC:3.1.3.86]
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04392  RAC1; Ras-related C3 botulinum toxin substrate 1
K04393  CDC42; cell division control protein 42
K04409  PAK1; p21-activated kinase 1 [EC:2.7.11.1]
K04438  CRK, CRKII; C-crk adapter molecule crk
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04688  RPS6KB; ribosomal protein S6 kinase beta [EC:2.7.11.1]
K04718  SPHK; sphingosine kinase [EC:2.7.1.91]
K05730  VAV; guanine nucleotide exchange factor VAV
K05743  LIMK1; LIM domain kinase 1 [EC:2.7.11.1]
K05744  LIMK2; LIM domain kinase 2 [EC:2.7.11.1]
K05747  WAS; Wiskott-Aldrich syndrome protein
K05748  WASF2; WAS protein family, member 2
K05753  WASF1; WAS protein family, member 1
K05754  ARPC5; actin related protein 2/3 complex, subunit 5
K05755  ARPC4; actin related protein 2/3 complex, subunit 4
K05756  ARPC3; actin related protein 2/3 complex, subunit 3
K05757  ARPC1A_B; actin related protein 2/3 complex, subunit 1A/1B
K05758  ARPC2; actin related protein 2/3 complex, subunit 2
K05765  CFL; cofilin
K05768  GSN; gelsolin
K05854  LYN; tyrosine-protein kinase Lyn [EC:2.7.10.2]
K05855  SYK; spleen tyrosine kinase [EC:2.7.10.2]
K05859  PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11]
K06068  PRKCD; novel protein kinase C delta type [EC:2.7.11.13]
K06083  WASF3; WAS protein family, member 3
K06274  VASP; vasodilator-stimulated phosphoprotein
K06463  FCGR3, CD16; low affinity immunoglobulin gamma Fc receptor III
K06472  FCGR2A, CD32; low affinity immunoglobulin gamma Fc receptor II-a
K06478  PTPRC, CD45; receptor-type tyrosine-protein phosphatase C [EC:3.1.3.48]
K06498  FCGR1A, CD64; high affinity immunoglobulin gamma Fc receptor I
K06856  IGH; immunoglobulin heavy chain
K07362  LAT; linker for activation of T cells family member 1
K07860  RAC2; Ras-related C3 botulinum toxin substrate 2
K07941  ARF6; ADP-ribosylation factor 6
K08011  NCF1, P47PHOX; neutrophil cytosolic factor 1
K08091  GAB2; GRB2-associated-binding protein 2
K08893  HCK; hemopoietic cell kinase [EC:2.7.10.2]
K12488  ASAP; Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein
K12559  MYO10; myosin X
K12560  FCGR2B, CD32; low affinity immunoglobulin gamma Fc receptor II-b
K12561  MARCKS; myristoylated alanine-rich C-kinase substrate
K12562  AMPH; amphiphysin
K13536  MARCKSL1, MRP; MARCKS-related protein
K13708  DOCK1; dedicator of cytokinesis protein 1
K15909  SHIP2, INPPL1; phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2 [EC:3.1.3.86]
K16342  PLA2G4, CPLA2; cytosolic phospholipase A2 [EC:3.1.1.4]
K16343  PLA2G6, IPLA2; calcium-independent phospholipase A2 [EC:3.1.1.4]
K17260  ACTR2, ARP2; actin-related protein 2
K18050  PRKCE; novel protein kinase C epsilon type [EC:2.7.11.13]
K18584  ACTR3, ARP3; actin-related protein 3
K19662  PRKCB; classical protein kinase C beta type [EC:2.7.11.13]
K19663  PRKCG; classical protein kinase C gamma type [EC:2.7.11.13]
K23484  DNM2; dynamin 2
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
ko04020  Calcium signaling pathway
ko04142  Lysosome
ko04144  Endocytosis
ko04810  Regulation of actin cytoskeleton

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