KEGG   PATHWAY: mlx04666
Entry
mlx04666                    Pathway                                
Name
Fc gamma R-mediated phagocytosis - Mirounga leonina (Southern elephant seal)
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
mlx04666  Fc gamma R-mediated phagocytosis
mlx04666

Other DBs
GO: 0006909
Organism
Mirounga leonina (Southern elephant seal) [GN:mlx]
Gene
117997741  DOCK1; dedicator of cytokinesis protein 1 isoform X1 [KO:K13708]
117997993  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
117998144  VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274]
117998224  SPHK2; sphingosine kinase 2 isoform X1 [KO:K04718] [EC:2.7.1.91]
117998687  PLA2G6; 85/88 kDa calcium-independent phospholipase A2 isoform X1 [KO:K16343] [EC:3.1.1.4]
117998715  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
117998914  [KO:K05756]
117999123  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
117999338  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
117999364  ARPC1A; actin-related protein 2/3 complex subunit 1A [KO:K05757]
117999367  ARPC1B; actin-related protein 2/3 complex subunit 1B [KO:K05757]
117999499  LIMK1; LIM domain kinase 1 isoform X1 [KO:K05743] [EC:2.7.11.1]
117999511  NCF1; neutrophil cytosol factor 1 [KO:K08011]
117999637  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
117999664  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
117999812  CRKL; crk-like protein [KO:K04438]
117999826  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
117999965  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
118000335  PIP5K1A; phosphatidylinositol 4-phosphate 5-kinase type-1 alpha isoform X1 [KO:K00889] [EC:2.7.1.68]
118000549  MARCKS; myristoylated alanine-rich C-kinase substrate [KO:K12561]
118001060  [KO:K05756]
118001589  WASF1; wiskott-Aldrich syndrome protein family member 1 [KO:K05753]
118002024  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118002026  ARF6; ADP-ribosylation factor 6 isoform X1 [KO:K07941]
118002823  [KO:K05765]
118002873  [KO:K05765]
118003270  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
118003295  PLA2G4F; cytosolic phospholipase A2 zeta [KO:K16342] [EC:3.1.1.4]
118003336  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
118003418  [KO:K16342] [EC:3.1.1.4]
118003546  PLA2G4D; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
118003930  GAB2; LOW QUALITY PROTEIN: GRB2-associated-binding protein 2 [KO:K08091]
118003941  CFL2; LOW QUALITY PROTEIN: cofilin-2 [KO:K05765]
118003950  INPPL1; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2 isoform X1 [KO:K15909] [EC:3.1.3.86]
118004217  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
118004424  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
118004774  [KO:K04393]
118004859  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
118005176  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
118005337  PLPP2; phospholipid phosphatase 2 [KO:K01080] [EC:3.1.3.4]
118005431  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
118005519  PIP5K1C; phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [KO:K00889] [EC:2.7.1.68]
118005672  DNM2; dynamin-2 isoform X1 [KO:K23484]
118005822  ARPC4; actin-related protein 2/3 complex subunit 4 [KO:K05755]
118006042  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
118006158  MYO10; unconventional myosin-X [KO:K12559]
118006301  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
118006556  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
118007274  [KO:K12488]
118007326  [KO:K12488]
118008048  ACTR2; actin-related protein 2 isoform X1 [KO:K17260]
118008176  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
118009565  WASF3; wiskott-Aldrich syndrome protein family member 3 isoform X1 [KO:K06083]
118010043  WAS; wiskott-Aldrich syndrome protein [KO:K05747]
118011341  HCK; tyrosine-protein kinase HCK isoform X1 [KO:K08893] [EC:2.7.10.2]
118011345  [KO:K04393]
118011488  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
118011925  INPP5D; phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 1 [KO:K03084] [EC:3.1.3.86]
118012053  ARPC2; actin-related protein 2/3 complex subunit 2 [KO:K05758]
118012523  ACTR3; actin-related protein 3 [KO:K18584]
118012565  BIN1; myc box-dependent-interacting protein 1 isoform X1 [KO:K12562]
118014023  FCGR3A; low affinity immunoglobulin gamma Fc region receptor III-A isoform X1 [KO:K06463]
118014025  FCGR2B; low affinity immunoglobulin gamma Fc region receptor II-b isoform X1 [KO:K12560]
118014237  PTPRC; receptor-type tyrosine-protein phosphatase C isoform X1 [KO:K06478] [EC:3.1.3.48]
118014382  ARPC5; actin-related protein 2/3 complex subunit 5 [KO:K05754]
118014408  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
118014553  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118014834  LYN; tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
118015218  ASAP1; arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 isoform X1 [KO:K12488]
118016067  CFL1; cofilin-1 [KO:K05765]
118016129  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
118016791  PLPP1; phospholipid phosphatase 1 isoform X1 [KO:K01080] [EC:3.1.3.4]
118016863  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
118017539  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
118017688  ARPC5L; actin-related protein 2/3 complex subunit 5-like protein [KO:K05754]
118017741  GSN; gelsolin isoform X1 [KO:K05768]
118017874  [KO:K05756]
118018155  [KO:K04392]
118018453  ARPC3; actin-related protein 2/3 complex subunit 3 isoform X1 [KO:K05756]
118018669  LIMK2; LIM domain kinase 2 isoform X1 [KO:K05744] [EC:2.7.11.1]
118019063  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
118019368  PLPP3; phospholipid phosphatase 3 [KO:K01080] [EC:3.1.3.4]
118019468  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
118019747  MARCKSL1; MARCKS-related protein [KO:K13536]
118019818  WASF2; wiskott-Aldrich syndrome protein family member 2 [KO:K05748]
118019897  ASAP3; LOW QUALITY PROTEIN: arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3 [KO:K12488]
118019913  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
118020028  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118020689  [KO:K05757]
118020814  SCIN; adseverin [KO:K05768]
118022658  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118023528  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
118024239  SPHK1; sphingosine kinase 1 isoform X1 [KO:K04718] [EC:2.7.1.91]
118024347  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
118024557  AMPH; amphiphysin isoform X1 [KO:K12562]
118024673  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
118025226  CRK; adapter molecule crk isoform X1 [KO:K04438]
118026076  [KO:K05758]
118026317  PIP5K1B; phosphatidylinositol 4-phosphate 5-kinase type-1 beta isoform X1 [KO:K00889] [EC:2.7.1.68]
118026369  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
118026829  ACTR3B; actin-related protein 3B isoform X1 [KO:K18584]
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
mlx04020  Calcium signaling pathway
mlx04142  Lysosome
mlx04144  Endocytosis
mlx04810  Regulation of actin cytoskeleton
KO pathway
ko04666   

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