Fc epsilon RI signaling pathway - Homo sapiens (human)

Curator(s): Julie Conway

Fc epsilon RI-mediated signaling pathways in mast cells are initiated by the interaction of antigen (Ag) with IgE bound to the extracellular domain of the alpha chain of Fc epsilon RI. The activation pathways are regulated both positively and negatively by the interactions of numerous signaling molecules. Mast cells that are thus activated release preformed granules which contain biogenic amines (especially histamines) and proteoglycans (especially heparin). The activation of phospholipase A2 causes the release of membrane lipids followed by development of lipid mediators such as leukotrienes (LTC4, LTD4 and LTE4) and prostaglandins (especially PDG2). There is also secretion of cytokines, the most important of which are TNF-alpha, IL-4 and IL-5. These mediators and cytokines contribute to inflammatory responses.    
Zoom out 50% Move left to zoom out, right to zoom in Zoom in 50% 100%

Fc epsilon RI signaling pathway - Homo sapiens (human) cluster_Membrane Membrane cluster_Degranulation Degranulation cluster_node34 Cytokine gene transcription cluster_node35 Generation of eicosanoids Antigen node1 IgE(1) Antigen->node1 node2 IgE(2) Antigen->node2 node3 FcERIa FcERIB FcERIy node1->node3 node4 FcERIa FcERIB FcERIy node2->node4 v-yes-1 Yamaguchi sarcoma viral related oncogene homolog LYN spleen tyrosine kinase SYK LYN->SYK +p Bruton agammaglobulinemia tyrosine kinase BTK LYN->BTK +p FYN oncogene related to SRC,FGR,YES FYN LYN->FYN LYN->node3 +p GRB2-associated binding protein 2 GAB2 SYK->GAB2 node6 SLP-76 SYK->node6 +p PI3K SYK->PI3K +p PLCy SYK->PLCy +p VAV SYK->VAV +p linker for activation of T cells LAT SYK->LAT +p PIP3 BTK->PIP3 BTK->PLCy +p node5 3 PIP3->node5 PIP3 PIP3->PLCy SHIP SHIP->PIP3 FYN->GAB2 +p GAB2->PI3K node6->VAV node7 12 PI3K->PIP3 PI3K->node7 PI3K PI3K->PLCy RAC PI3K->RAC pyruvate dehydrogenase kinase,isozyme 1 PDK1 PI3K->PDK1 IP3 PLCy->IP3 DAG PLCy->DAG VAV->RAC node8 1 LAT->node8 LAT growth factor receptor-bound protein 2 GRB2 LAT->GRB2 SOS GRB2->SOS node9 2 SOS->node9 SOS RAS SOS->RAS node10 1 RAS->node10 RAS node12 RAF-1 RAS->node12 node11 2 node12->node11 RAF-1 MEK node12->MEK +p node13 2 MEK->node13 MEK ERK MEK->ERK +p node14 24 ERK->node14 ERK DNA ERK->DNA cPLA2 ERK->cPLA2 node15 MKK4/7 RAC->node15 node20 MKK3/6 RAC->node20 JNK node15->JNK +p node16 11 JNK->node16 JNK JNK->DNA node28 1 DNA->node28 AKT PDK1->AKT +p node17 29 AKT->DNA AKT->node17 AKT node18 Ca2+ IP3->node18 PKC DAG->PKC node30 3 node18->node30 node19 5 PKC->DNA PKC->node19 PKC P38 node20->P38 +p node21 2 P38->DNA P38->node21 P38 Toxic to parasites Increase vascular permeability Cause smooth muscle contraction node27 22 Arachidonic acid cPLA2->Arachidonic acid node29 2 Arachidonic acid->node29 node26 GM-CSF node28->node26 node23 IL-13 node28->node23 node24 IL-3 node28->node24 node22 IL-4 node28->node22 node25 IL-5 node28->node25 TNFa node28->TNFa Stimulate and amplify Th2 cell response Promote eosinophil production and activation Promotes inflammation Stimulates cytokine production by many cell types Activates endothelium LTC4 node29->LTC4 LTD4 node29->LTD4 LTE4 node29->LTE4 PGD2 node29->PGD2 Heparin node30->Heparin Histamine node30->Histamine Recruit effector cells node31 4 node32 Cause smooth muscle contraction(2) node31->node32 Stimulate mucus secretion node31->Stimulate mucus secretion node33 Increase vascular permeability(2) node31->node33 node26->Promote eosinophil production and activation node23->Stimulate and amplify Th2 cell response node24->Promote eosinophil production and activation node22->Stimulate and amplify Th2 cell response node25->Promote eosinophil production and activation TNFa->node27 TNFa TNFa->Promotes inflammation TNFa->Stimulates cytokine production by many cell types TNFa->Activates endothelium LTC4->node31 LTD4->node31 LTE4->node31 PGD2->Recruit effector cells PGD2->node31 Heparin->Toxic to parasites Heparin->Increase vascular permeability Heparin->Cause smooth muscle contraction Histamine->Toxic to parasites Histamine->Increase vascular permeability Histamine->Cause smooth muscle contraction node3->SYK +p print "