KEGG   PATHWAY: rno04666
Entry
rno04666                    Pathway                                
Name
Fc gamma R-mediated phagocytosis - Rattus norvegicus (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
rno04666  Fc gamma R-mediated phagocytosis
rno04666

Other DBs
GO: 0006909
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
295279  Fcgr1a; high affinity immunoglobulin gamma Fc receptor I precursor [KO:K06498]
498276  Fcgr2al1; Fc gamma receptor 2A like 1 [KO:K06472]
134481532  low affinity immunoglobulin gamma Fc region receptor III isoform X1 [KO:K06472]
116591  Fcgr2a; low affinity immunoglobulin gamma Fc region receptor III isoform 1 [KO:K06463]
304966  Fcgr3a; low affinity immunoglobulin gamma Fc region receptor III-A precursor [KO:K06463]
24699  Ptprc; receptor-type tyrosine-protein phosphatase C isoform 4 precursor [KO:K06478] [EC:3.1.3.48]
25734  Hck; tyrosine-protein kinase HCK [KO:K08893] [EC:2.7.10.2]
81515  Lyn; tyrosine-protein kinase Lyn isoform A [KO:K05854] [EC:2.7.10.2]
25155  Syk; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
134484121  LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [KO:K00922] [EC:2.7.1.153]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
83840  Rps6kb1; ribosomal protein S6 kinase beta-1 [KO:K04688] [EC:2.7.11.1]
361696  Rps6kb2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
25738  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
29337  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
170538  Prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
29340  Prkce; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
296091  Pla2g4e; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:3.1.1.4]
24653  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
311341  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
691905  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
691907  Pla2g4f; cytosolic phospholipase A2 zeta isoform X1 [KO:K16342] [EC:3.1.1.4]
691810  Pla2g4c; cytosolic phospholipase A2 gamma [KO:K16342] [EC:3.1.1.4]
360426  Pla2g6; 85/88 kDa calcium-independent phospholipase A2 isoform 1 [KO:K16343] [EC:3.1.1.4]
25603  Marcks; myristoylated alanine-rich C-kinase substrate [KO:K12561]
81520  Marcksl1; MARCKS-related protein [KO:K13536]
103689966  MARCKS-related protein-like [KO:K13536]
25097  Pld2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
25096  Pld1; phospholipase D1 isoform 2 [KO:K01115] [EC:3.1.4.4]
64369  Plpp1; phospholipid phosphatase 1 [KO:K01080] [EC:3.1.3.4]
246115  Plpp2; phospholipid phosphatase 2 [KO:K01080] [EC:3.1.3.4]
192270  Plpp3; phospholipid phosphatase 3 [KO:K01080] [EC:3.1.3.4]
308589  Sphk2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
170897  Sphk1; sphingosine kinase 1 isoform b [KO:K04718] [EC:2.7.1.91]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:2.7.11.13]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
114553  Ncf1; neutrophil cytosolic factor 1 [KO:K08011]
296654  Gsn; gelsolin precursor [KO:K05768]
298975  Scin; scinderin [KO:K05768]
25156  Vav1; proto-oncogene vav [KO:K05730]
295378  Vav3; guanine nucleotide exchange factor VAV3 [KO:K05730]
296603  Vav2; guanine nucleotide exchange factor VAV2 [KO:K05730]
64465  Cdc42; cell division control protein 42 homolog [KO:K04393]
361517  Vasp; vasodilator-stimulated phosphoprotein [KO:K06274]
289820  Actr2; actin-related protein 2 [KO:K17260]
362298  Actr3b; actin-related protein 3B [KO:K18584]
81732  Actr3; actin-related protein 3 [KO:K18584]
54227  Arpc1b; actin-related protein 2/3 complex subunit 1B [KO:K05757]
81824  Arpc1a; actin-related protein 2/3 complex subunit 1A [KO:K05757]
301511  Arpc2; actin-related protein 2/3 complex subunit 2 [KO:K05758]
288669  Arpc3; actin-related protein 2/3 complex subunit 3 [KO:K05756]
297518  Arpc4; actin-related protein 2/3 complex subunit 4 [KO:K05755]
296710  Arpc5l; actin-related protein 2/3 complex subunit 5-like protein [KO:K05754]
360854  Arpc5; actin-related protein 2/3 complex subunit 5 [KO:K05754]
363875  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
366957  Rac2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
294568  Wasf1; actin-binding protein WASF1 [KO:K05753]
313024  Wasf2; actin-binding protein WASF2 [KO:K05748]
682937  Wasf3; WASP family member 3 [KO:K06083]
29431  Pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
65172  Limk1; LIM domain kinase 1 [KO:K05743] [EC:2.7.11.1]
29524  Limk2; LIM domain kinase 2 [KO:K05744] [EC:2.7.11.1]
29271  Cfl1; cofilin-1 [KO:K05765]
366624  Cfl2; cofilin-2 [KO:K05765]
688430  Cfl1l1; cofilin-1-like [KO:K05765]
309419  Pip5k1b; phosphatidylinositol 4-phosphate 5-kinase type-1 beta [KO:K00889] [EC:2.7.1.68]
314641  Pip5k1c; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform c [KO:K00889] [EC:2.7.1.68]
365865  Pip5k1a; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha [KO:K00889] [EC:2.7.1.68]
79121  Arf6; ADP-ribosylation factor 6 [KO:K07941]
54245  Crk; adapter molecule crk [KO:K04438]
287942  Crkl; crk-like protein [KO:K04438]
309081  Dock1; dedicator of cytokinesis protein 1 [KO:K13708]
684122  Asap3; arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3 isoform X1 [KO:K12488]
314961  Asap1; arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 [KO:K12488]
362719  Asap2; arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 2 [KO:K12488]
289211  Fcgr2b; low affinity immunoglobulin gamma Fc region receptor II [KO:K12560]
54259  Inpp5d; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 [KO:K03084] [EC:3.1.3.86]
65038  Inppl1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform 1 [KO:K15909] [EC:3.1.3.86]
84477  Gab2; GRB2-associated-binding protein 2 [KO:K08091]
81511  Lat; linker for activation of T-cells family member 1 [KO:K07362]
25751  Dnm2; dynamin-2 [KO:K23484] [EC:3.6.5.5]
60668  Amph; amphiphysin [KO:K12562]
117028  Bin1; myc box-dependent-interacting protein 1 [KO:K12562]
310178  Myo10; unconventional 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
  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
  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
  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
  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
  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
  Authors
Kwiatkowska K, Sobota A
  Title
Signaling pathways in phagocytosis.
  Journal
Reference
  Authors
Greenberg S
  Title
Modular components of phagocytosis.
  Journal
J Leukoc Biol 66:712-7 (1999)
DOI:10.1002/jlb.66.5.712
Reference
  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
  Authors
May RC, Machesky LM
  Title
Phagocytosis and the actin cytoskeleton.
  Journal
J Cell Sci 114:1061-77 (2001)
Reference
  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
  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
  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
  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
  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
  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
  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
  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
rno04020  Calcium signaling pathway
rno04142  Lysosome
rno04144  Endocytosis
rno04810  Regulation of actin cytoskeleton
KO pathway
ko04666   

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