Chemokine signaling pathway - Homo sapiens (human)

Curator(s): Joe Strothman

Inflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for the cell trafficking and thus are vital for protective host response. In addition, chemokines regulate plethora of biological processes of hematopoietic cells to lead cellular activation, differentiation and survival. The chemokine signal is transduced by chemokine receptors (G-protein coupled receptors) expressed on the immune cells. After receptor activation, the alpha- and beta-gamma-subunits of G protein dissociate to activate diverse downstream pathways resulting in cellular polarization and actin reorganization. Various members of small GTPases are involved in this process. Induction of nitric oxide and production of reactive oxygen species are as well regulated by chemokine signal via calcium mobilization and diacylglycerol production.    
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Chemokine signaling pathway - Homo sapiens (human) cluster_chemokine chemokine cluster_chemokineR chemokineR cluster_node36 !js cluster_node37 !end cluster_node38 !map cluster_node39 G B gamma cluster_node40 !reg node1 4 node2 1 node6 2 node7 JAK2/3 node7->node6 JAK2/3 STAT node7->STAT +p node8 5 GaI AC GaI->AC v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) SRC GaI->SRC node30 4 GaI->node30 cAMP AC->cAMP node10 2 SRC->node10 SRC SHC SRC->SHC +p PI3K SRC->PI3K +p node32 DOCK2 ELMO1 SRC->node32 +p IL2-inducible T-cell kinase ITK SRC->ITK Pyk2 SRC->Pyk2 +p FAK SRC->FAK +p PKA cAMP->PKA node11 1 PKA->node11 PKA growth factor receptor-bound protein 2 GRB2 SHC->GRB2 SOS GRB2->SOS node12 2 SOS->node12 SOS Ras SOS->Ras node13 1 node14 4 Raf Raf->node14 Raf MEK1 Raf->MEK1 +p GRK node4 2 GRK->node4 +p node15 B-arrestin node16 12 PI3K->node16 PI3K PKCzeta PI3K->PKCzeta PIP3 PI3K->PIP3 PI3K->ITK PI3K->FAK +p PI3K->Ras node17 2 MEK1->node17 MEK1 node19 ERK1/2 MEK1->node19 +p node18 15 node19->node18 ERK1/2 DNA node19->DNA PKCzeta->node19 node20 3 PIP3->node20 PIP3 AKT PIP3->AKT node27 P-Rex1 PIP3->node27 node21 29 AKT->node21 AKT FOXO AKT->FOXO +p IKK AKT->IKK +p GSK3 AKT->GSK3 +p node22 1 FOXO->node22 FOXO FOXO->DNA node23 8 IKK->node23 IKK IkB IKK->IkB +p node24 4 IkB->node24 IkB Ubiquitin mediated proteolysis IkB->Ubiquitin mediated proteolysis NFkB IkB->NFkB node25 32 NFkB->node25 NFkB NFkB->DNA node26 6 GSK3->node26 GSK3 Rac node27->Rac p21 protein (Cdc42/Rac)-activated kinase 1 PAK1 Rac->PAK1 Regulation of actin cytoskeleton Rac->Regulation of actin cytoskeleton PAK1->Regulation of actin cytoskeleton node32->Rac Vav ITK->Vav Vav->Rac cell division cycle 42 (GTP binding protein,25kDa) CDC42 Vav->CDC42 ras homolog gene family,member A RHOA Vav->RHOA node33 TIAM1 PARD3 PRKCZ node33->Rac CDC42->PAK1 CDC42->node33 WASP CDC42->WASP WASP->Regulation of actin cytoskeleton ROCK RHOA->ROCK ROCK->Regulation of actin cytoskeleton Paxillin Pyk2->Paxillin v-crk sarcoma virus CT10 oncogene homolog (avian) CRK Pyk2->CRK Paxillin->Regulation of actin cytoskeleton CRK->Regulation of actin cytoskeleton FAK->Paxillin +p p130Cas FAK->p130Cas p130Cas->CRK PLCbeta IP3 PLCbeta->IP3 DAG PLCbeta->DAG node34 Ca2+ IP3->node34 PKC node34->PKC RAS guanyl releasing protein 2 (calcium and DAG-regulated) RASGRP2 node34->RASGRP2 DAG->PKC DAG->RASGRP2 node35 1 PKC->node35 PKC p47phox PKC->p47phox Degranulation PKC->Degranulation NO Induction PKC->NO Induction Chemotaxis PKC->Chemotaxis Rap1 RASGRP2->Rap1 Rap1->CDC42 ROS production p47phox->ROS production node3 1 node5 3 node3->node5 chemokineR A node5->chemokineR A chemokineR B node5->chemokineR B node4->node7 node4->GaI node4->node15 chemokineR A->node4 chemokineR B->node4 node30->PLCbeta node28 Gbeta-gamma 1 node30->node28 node29 Gbeta-gamma 2 node30->node29 node31 5 node28->node31 node29->node31 node31->PI3K node31->node27 STAT->node8 STAT STAT->DNA Ras->node13 Ras Ras->Raf chemokine A chemokine A->node1 chemokine A chemokine A->node3 chemokine B chemokine B->node2 chemokine B chemokine B->node3 chemokine C chemokine C->node3 node9 Jak -STAT signaling pathway - Homo sapiens MAPK Signaling Pathway Cell Survival Apoptosis Cytokine Leukocyte transendothelial migration Cell growth Migration print "