KEGG PATHWAY: hsa04666

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

Disease

H00098	Chronic granulomatous disease
H00698	Nemaline myopathy
H01240	Immune thrombocytopenia (ITP)
H01387	Activated PI3K-delta syndrome (APDS)

Other DBs

BSID:

114228

GO:

0006909

Organism

Homo sapiens (human) [GN:hsa]

Gene

102723407	IGH; putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
2209	FCGR1A; Fc fragment of IgG receptor Ia [KO:K06498]
2212	FCGR2A; Fc fragment of IgG receptor IIa [KO:K06472]
5788	PTPRC; protein tyrosine phosphatase, receptor type C [KO:K06478] [EC:3.1.3.48]
3055	HCK; HCK proto-oncogene, Src family tyrosine kinase [KO:K08893] [EC:2.7.10.2]
4067	LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
6850	SYK; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
5290	PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293	PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291	PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
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:2.7.11.1]
208	AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000	AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
6198	RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
6199	RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
5335	PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
5336	PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
5580	PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
5581	PRKCE; protein kinase C epsilon [KO:K18050] [EC:2.7.11.13]
5894	RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604	MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5594	MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595	MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
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:3.1.4.4]
5338	PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
8611	PLPP1; phospholipid phosphatase 1 [KO:K01080] [EC:3.1.3.4]
8613	PLPP3; phospholipid phosphatase 3 [KO:K01080] [EC:3.1.3.4]
8612	PLPP2; phospholipid phosphatase 2 [KO:K01080] [EC:3.1.3.4]
8877	SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
56848	SPHK2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
5578	PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
5579	PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
5582	PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
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; Wiskott-Aldrich syndrome [KO:K05747]
8976	WASL; Wiskott-Aldrich syndrome like [KO:K05747]
7408	VASP; vasodilator stimulated phosphoprotein [KO:K06274]
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]
10093	ARPC4; actin related protein 2/3 complex subunit 4 [KO:K05755]
10094	ARPC3; actin related protein 2/3 complex subunit 3 [KO:K05756]
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]
5879	RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
5880	RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
8936	WASF1; WAS protein family member 1 [KO:K05753]
10163	WASF2; WAS protein family member 2 [KO:K05748]
10810	WASF3; WAS protein family member 3 [KO:K06083]
5058	PAK1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
3984	LIMK1; LIM domain kinase 1 [KO:K05743] [EC:2.7.11.1]
3985	LIMK2; LIM domain kinase 2 [KO:K05744] [EC:2.7.11.1]
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:2.7.1.68]
8394	PIP5K1A; phosphatidylinositol-4-phosphate 5-kinase type 1 alpha [KO:K00889] [EC:2.7.1.68]
8395	PIP5K1B; phosphatidylinositol-4-phosphate 5-kinase type 1 beta [KO:K00889] [EC:2.7.1.68]
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]
1794	DOCK2; dedicator of cytokinesis 2 [KO:K12367]
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 fragment of IgG receptor IIb [KO:K12560]
3635	INPP5D; inositol polyphosphate-5-phosphatase D [KO:K03084] [EC:3.1.3.86]
3636	INPPL1; inositol polyphosphate phosphatase like 1 [KO:K15909] [EC:3.1.3.86]
9846	GAB2; GRB2 associated binding protein 2 [KO:K08091]
27040	LAT; linker for activation of T-cells [KO:K07362]
273	AMPH; amphiphysin [KO:K12562]
274	BIN1; bridging integrator 1 [KO:K12562]
4651	MYO10; myosin X [KO:K12559]
100137049	PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
123745	PLA2G4E; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
1785	DNM2; dynamin 2 [KO:K01528] [EC:3.6.5.5]
2214	FCGR3A; Fc fragment of IgG receptor IIIa [KO:K06463]
255189	PLA2G4F; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
283748	PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
5321	PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
8398	PLA2G6; phospholipase A2 group VI [KO:K16343] [EC:3.1.1.4]

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)

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)

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)

Reference

Authors

Rosales C (ed).

Title

Molecular Mechanisms of Phagocytosis

Journal

Springer (2005)

KO pathway

ko04666

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Pathway (1)   
   BioSystems (1)   
Disease (4)   
   KEGG DISEASE (4)   
Genome (1)   
   KEGG GENOME (1)   
Gene (91)   
   KEGG GENES (91)   
All databases (97)   

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