KEGG   PATHWAY: ngi04666
Entry
ngi04666                    Pathway                                
Name
Fc gamma R-mediated phagocytosis - Nannospalax galili (Upper Galilee mountains blind mole rat)
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
ngi04666  Fc gamma R-mediated phagocytosis
ngi04666

Other DBs
GO: 0006909
Organism
Nannospalax galili (Upper Galilee mountains blind mole rat) [GN:ngi]
Gene
103751925  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
103726091  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
103742641  Fcgr1a; high affinity immunoglobulin gamma Fc receptor I [KO:K06498]
103746769  Fcgr2a; Fc fragment of IgG receptor IIa [KO:K06472]
103746771  low affinity immunoglobulin gamma Fc region receptor III-like [KO:K06463]
103731886  Ptprc; protein tyrosine phosphatase, receptor type C [KO:K06478] [EC:3.1.3.48]
103731073  Hck; HCK proto-oncogene, Src family tyrosine kinase [KO:K08893] [EC:2.7.10.2]
103734185  Lyn; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
103745419  Syk; spleen associated tyrosine kinase [KO:K05855] [EC:2.7.10.2]
103738596  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103733121  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103742946  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103738715  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103726879  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103730305  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103746884  Akt3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103750757  Akt2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103752536  Akt1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103741760  Rps6kb1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:2.7.11.1]
103725586  Rps6kb2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:2.7.11.1]
103747244  Plcg1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
103748739  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
103725694  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2-like [KO:K05859] [EC:3.1.4.11]
103749021  Prkcd; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
103725757  Prkce; protein kinase C epsilon [KO:K18050] [EC:2.7.11.13]
103751450  Raf1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103736801  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103741442  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103726390  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103744946  Pla2g4d; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
103744945  Pla2g4e; phospholipase A2 group IVE [KO:K16342] [EC:3.1.1.4]
103744942  Pla2g4b; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
103744947  Pla2g4f; phospholipase A2 group IVF [KO:K16342] [EC:3.1.1.4]
103726649  Pla2g4a; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
103732429  Pla2g4c; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]
103748592  Pla2g6; phospholipase A2 group VI [KO:K16343] [EC:3.1.1.4]
103733787  Marcks; myristoylated alanine rich protein kinase C substrate [KO:K12561]
103745912  Marcksl1; MARCKS like 1 [KO:K13536]
103752195  Pld2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
103731722  Pld1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
103734095  Plpp3; phospholipid phosphatase 3 [KO:K01080] [EC:3.1.3.4]
103737371  Plpp2; phospholipid phosphatase 2 [KO:K01080] [EC:3.1.3.4]
103739918  Plpp1; phospholipid phosphatase 1 [KO:K01080] [EC:3.1.3.4]
103732783  Sphk1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
103742305  sphingosine kinase 1-like [KO:K04718] [EC:2.7.1.91]
103743619  Sphk2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
103742202  Prkca; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
103746928  Prkcb; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
103729666  Prkcg; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
103748483  Ncf1; neutrophil cytosolic factor 1 [KO:K08011]
103734490  Gsn; gelsolin [KO:K05768]
103730156  Scin; scinderin [KO:K05768]
103737178  Vav1; vav guanine nucleotide exchange factor 1 [KO:K05730]
103742820  Vav2; vav guanine nucleotide exchange factor 2 [KO:K05730]
103745151  guanine nucleotide exchange factor VAV3 [KO:K05730]
103730717  Vav3; vav guanine nucleotide exchange factor 3 [KO:K05730]
103746394  Cdc42; cell division cycle 42 [KO:K04393]
103741643  Was; Wiskott-Aldrich syndrome [KO:K05747]
103749195  Vasp; vasodilator-stimulated phosphoprotein [KO:K06274]
103749563  Actr2; ARP2 actin related protein 2 homolog [KO:K17260]
103735321  Actr3; ARP3 actin related protein 3 homolog [KO:K18584]
103745329  Actr3b; ARP3 actin related protein 3 homolog B [KO:K18584]
103726464  Arpc1a; actin related protein 2/3 complex subunit 1A [KO:K05757]
103726465  Arpc1b; actin related protein 2/3 complex subunit 1B [KO:K05757]
103727709  Arpc2; actin related protein 2/3 complex subunit 2 [KO:K05758]
103739080  Arpc3; actin related protein 2/3 complex subunit 3 [KO:K05756]
103751421  Arpc4; actin related protein 2/3 complex subunit 4 [KO:K05755]
103726672  Arpc5; actin related protein 2/3 complex subunit 5 [KO:K05754]
103726954  Arpc5l; actin related protein 2/3 complex subunit 5 like [KO:K05754]
103726484  Rac1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
103748617  Rac2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
103749551  Wasf1; WAS protein family member 1 [KO:K05753]
103737074  Wasf2; WAS protein family member 2 [KO:K05748]
103731011  Wasf3; WAS protein family member 3 [KO:K06083]
103743005  Pak1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
103748493  Limk1; LIM domain kinase 1 [KO:K05743] [EC:2.7.11.1]
103740428  Limk2; LIM domain kinase 2 [KO:K05744] [EC:2.7.11.1]
103731431  Cfl2; cofilin 2 [KO:K05765]
103725002  Cfl1; cofilin 1 [KO:K05765]
103737261  Pip5k1c; phosphatidylinositol-4-phosphate 5-kinase type 1 gamma [KO:K00889] [EC:2.7.1.68]
103749401  Pip5k1b; phosphatidylinositol-4-phosphate 5-kinase type 1 beta [KO:K00889] [EC:2.7.1.68]
103730072  Pip5k1a; phosphatidylinositol-4-phosphate 5-kinase type 1 alpha [KO:K00889] [EC:2.7.1.68]
103731519  Arf6; ADP ribosylation factor 6 [KO:K07941]
103741458  Crkl; CRK like proto-oncogene, adaptor protein [KO:K04438]
103730505  Crk; CRK proto-oncogene, adaptor protein [KO:K04438]
103744273  dedicator of cytokinesis protein 1-like [KO:K13708]
103733379  dedicator of cytokinesis protein 1 [KO:K13708]
103743922  Asap1; ArfGAP with SH3 domain, ankyrin repeat and PH domain 1 [KO:K12488]
103746410  Asap3; ArfGAP with SH3 domain, ankyrin repeat and PH domain 3 [KO:K12488]
103747632  Asap2; ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 [KO:K12488]
103746773  Fcgr2b; Fc fragment of IgG receptor IIb [KO:K12560]
103738235  Inpp5d; inositol polyphosphate-5-phosphatase D [KO:K03084] [EC:3.1.3.86]
103750804  Inppl1; inositol polyphosphate phosphatase like 1 [KO:K15909] [EC:3.1.3.86]
103742992  Gab2; GRB2 associated binding protein 2 [KO:K08091]
103726413  Lat; linker for activation of T-cells [KO:K07362]
103747545  Dnm2; dynamin 2 [KO:K23484] [EC:3.6.5.5]
103732133  Bin1; bridging integrator 1 [KO:K12562]
103745062  Amph; amphiphysin [KO:K12562]
103724636  Myo10; myosin X [KO:K12559]
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
ngi04020  Calcium signaling pathway
ngi04142  Lysosome
ngi04144  Endocytosis
ngi04810  Regulation of actin cytoskeleton
KO pathway
ko04666   
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