Fc gamma R-mediated phagocytosis - Homo sapiens (human)

Curator(s): Joe Strothman

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.    
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Fc gamma R-mediated phagocytosis - Homo sapiens (human) cluster_node19 Neutrophil Macrophage Monocyte cluster_node20 Phagocytosis 2 cluster_node21 Phagocytosis 1 cluster_Bacterium Bacterium cluster_Ca Ca cluster_node22 !Ca2 cluster_node23 NADPH oxidase cluster_node24 Respiratory burst of phagosome IgG Fc fragment of IgG,low affinity IIa,receptor (CD32) FCGR2A IgG->FCGR2A Fc fragment of IgG,high affinity Ia,receptor (CD64) FCGR1A IgG->FCGR1A Fc fragment of IgG,low affinity IIIa,receptor (CD16a) FCGR3A IgG->FCGR3A SHIP node16 1 SHIP->node16 node1 2 v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC SRC->node1 SRC GRB2-associated binding protein 2 GAB2 SRC->GAB2 +p SRC->FCGR2A +p spleen tyrosine kinase SYK PI3K SYK->PI3K +p PLD SYK->PLD ADP-ribosylation factor 6 ARF6 SYK->ARF6 PLCG SYK->PLCG +p Vav SYK->Vav GAB2->PI3K node2 1 linker for activation of T cells LAT LAT->node2 LAT LAT->PI3K node3 12 PI3K->node3 PI3K PI3K->PLCG Dynamin2 PI3K->Dynamin2 PI3K->node16 node4 3 PIP3 PIP3->node4 PIP3 PIP3->PLD PIP3->PLCG MyosinX PIP3->MyosinX AKT PIP3->AKT PA PLD->PA SPHK PLD->SPHK ARF6->PLD PIP5k ARF6->PIP5k PAP PA->PAP PA->PIP5k DAG PLCG->DAG IP3 PLCG->IP3 Phagocytosis 1 Dynamin2->Phagocytosis 1 amphiphysin AMPH AMPH->Dynamin2 MyosinX->Phagocytosis 1 node5 29 AKT->node5 AKT p70S6K AKT->p70S6K PKC DAG->PKC PAP->DAG node17 2 IP3->node17 PIP2 PIP5k->PIP2 node6 Cdc-42 node14 WASP VASP node6->node14 p70S6K->Phagocytosis 1 node7 1 PKC->node7 PKC myristoylated alanine-rich protein kinase C substrate MARCKS PKC->MARCKS +p v-raf-1 murine leukemia viral oncogene homolog 1 RAF1 PKC->RAF1 iPLA2 PKC->iPLA2 MARCKS->Phagocytosis 1 node8 2 RAF1->node8 RAF1 MEK RAF1->MEK +p node9 2 MEK->node9 MEK node11 ERK1/2 MEK->node11 +p node10 15 node11->node10 ERK1/2 cPLA2 node11->cPLA2 AA cPLA2->AA AA->Phagocytosis 1 iPLA2->AA node13 4 cPKC cPKC->iPLA2 cPKC->node13 cPKC p47phox cPKC->p47phox Gelsolin Phagocytosis 2 Gelsolin->Phagocytosis 2 node15 Arp2/3 node14->node15 Vav->node6 Rac Vav->Rac CrkII dedicator of cytokinesis 2 DOCK2 CrkII->DOCK2 DOCK2->Rac Rac->PIP5k WAVE Rac->WAVE p21 protein (Cdc42/Rac)-activated kinase 1 PAK1 Rac->PAK1 ARF6 2 Rac->ARF6 2 PAG3 PAG3->ARF6 2 WAVE->node15 node15->Phagocytosis 2 LIMK PAK1->LIMK +p Cofilin LIMK->Cofilin +p Cofilin->Phagocytosis 2 ARF6 2->Phagocytosis 2 node16->PIP3 PIP2->Gelsolin PIP2->node14 node12 Ca2+ node17->node12 node12->cPKC node12->Gelsolin Antigen Antigen->IgG CD45 CD45->SRC -p FCGR2A->SYK FCGR2A->CrkII Fc fragment of IgG,low affinity IIb,receptor (CD32) FCGR2B FCGR2B->SHIP Digestion of bacterium p47phox->Digestion of bacterium Particle internalization 2 Pseudopod extention Lysosome Membrane Remodeling Calcium signaling pathway Phagosome closure Focal exocytosis Membrane trafficking Regulation of actin cytoskeleton 1 Particle internalization Endocytosis node18 Phagosome-lysosome fusion Regulation of actin cytoskeleton 2 print "