Entry
Name
Chemokine signaling pathway - Homo sapiens (human)
Description
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.
Class
Organismal Systems; Immune system
BRITE hierarchy
Pathway map
Ortholog table
Network
Element
N00152 CXCR-GNB/G-ERK signaling pathway
N00153 CCR/CXCR-GNB/G-PI3K-RAC signaling pathway
N00154 CXCR-GNB/G-PI3K-AKT signaling pathway
N00399 CCR2-GNB/G-PI3K-NFKB signaling pathway
N00401 CXCR4-GNAQ-PLCB/G-calcineurin signaling pathway
N00403 CX3CR1-GNAI-AC-PKA signaling pathway
N00413 CXCR4-GNB/G-PLCB-PKC signaling pathway
N00428 CCR5-GNB/G-PLCB/G-PKC signaling pathway
N00430 CXCR4-GNAI-PI3K-BAD signaling pathway
N00433 CXCR4-GNB/G-RAC signaling pathway
N00546 CXCL12-CXCR4-PKC-ERK signaling pathaway
N01746 CCR/CXCR-GNB/G-PI3K signaling pathway
N01765 CXCR4-GNAQ-PLCB/G signaling pathway
N01766 CX3CR1-GNAI-AC signaling pathway
N01767 CXCR4-GNAI-Src signaling pathway
N01769 CCR5-GNB/G-PLCB/G signaling pathway
N01770 CCR2-GNB/G-PI3K signaling pathway
N01771 CXCR4-GNB/G signaling pathway
Drug
D06297 Vicriviroc maleate (USAN)
D06557 Aplaviroc hydrochloride (USAN)
D08971 Plerixafor (JAN/USAN/INN)
D09665 Saracatinib difumarate (USAN)
D09783 Tofacitinib citrate (JAN/USAN)
D09878 Cenicriviroc (USAN/INN)
D09879 Cenicriviroc mesylate (USAN)
D09960 Ruxolitinib phosphate (JAN/USAN)
D10308 Baricitinib (JAN/USAN/INN)
D10379 Vercirnon sodium (USAN)
D10420 Elubrixin tosylate (USAN)
D10972 Plozalizumab (USAN/INN)
D11046 Delgocitinib (JAN/USAN/INN)
D11323 Umbralisib tosylate (USAN)
D11354 Nemiralisib succinate (USAN)
D11742 Lazucirnon hydrochloride (USAN)
D11816 Belumosudil mesylate (USAN)
D11970 Ritlecitinib tosylate (USAN)
D11998 Ilacirnon sodium (USAN)
D12128 Balixafortide (USAN/INN)
D12281 Motixafortide (USAN/INN)
D12282 Motixafortide acetate (USAN)
D12884 Tivumecirnon (USAN/INN)
D12885 Tivumecirnon besylate (USAN)
D12993 Frevecitinib (USAN/INN)
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
2919 CXCL1; C-X-C motif chemokine ligand 1 [KO:K05505 ]
2920 CXCL2; C-X-C motif chemokine ligand 2 [KO:K05505 ]
2921 CXCL3; C-X-C motif chemokine ligand 3 [KO:K05505 ]
6372 CXCL6; C-X-C motif chemokine ligand 6 [KO:K05506 ]
6374 CXCL5; C-X-C motif chemokine ligand 5 [KO:K05506 ]
3576 CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030 ]
4283 CXCL9; C-X-C motif chemokine ligand 9 [KO:K05416 ]
3627 CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671 ]
6373 CXCL11; C-X-C motif chemokine ligand 11 [KO:K12672 ]
6387 CXCL12; C-X-C motif chemokine ligand 12 [KO:K10031 ]
10563 CXCL13; C-X-C motif chemokine ligand 13 [KO:K10032 ]
58191 CXCL16; C-X-C motif chemokine ligand 16 [KO:K10035 ]
5197 PF4V1; platelet factor 4 variant 1 [KO:K05407 ]
9547 CXCL14; C-X-C motif chemokine ligand 14 [KO:K10033 ]
6375 XCL1; X-C motif chemokine ligand 1 [KO:K05507 ]
6846 XCL2; X-C motif chemokine ligand 2 [KO:K05507 ]
6376 CX3CL1; C-X3-C motif chemokine ligand 1 [KO:K05508 ]
6346 CCL1; C-C motif chemokine ligand 1 [KO:K05514 ]
6347 CCL2; C-C motif chemokine ligand 2 [KO:K14624 ]
414062 CCL3L3; C-C motif chemokine ligand 3 like 3 [KO:K05408 ]
6348 CCL3; C-C motif chemokine ligand 3 [KO:K05408 ]
6349 CCL3L1; C-C motif chemokine ligand 3 like 1 [KO:K05408 ]
388372 CCL4L1; C-C motif chemokine ligand 4 like 1 [KO:K12964 ]
6351 CCL4; C-C motif chemokine ligand 4 [KO:K12964 ]
9560 CCL4L2; C-C motif chemokine ligand 4 like 2 [KO:K12964 ]
6352 CCL5; C-C motif chemokine ligand 5 [KO:K12499 ]
6354 CCL7; C-C motif chemokine ligand 7 [KO:K05509 ]
6355 CCL8; C-C motif chemokine ligand 8 [KO:K16596 ]
6356 CCL11; C-C motif chemokine ligand 11 [KO:K16597 ]
6357 CCL13; C-C motif chemokine ligand 13 [KO:K16595 ]
6358 CCL14; C-C motif chemokine ligand 14 [KO:K21092 ]
6359 CCL15; C-C motif chemokine ligand 15 [KO:K05511 ]
6368 CCL23; C-C motif chemokine ligand 23 [KO:K05511 ]
6360 CCL16; C-C motif chemokine ligand 16 [KO:K21093 ]
6361 CCL17; C-C motif chemokine ligand 17 [KO:K21083 ]
6362 CCL18; C-C motif chemokine ligand 18 [KO:K21094 ]
6363 CCL19; C-C motif chemokine ligand 19 [KO:K05512 ]
6364 CCL20; C-C motif chemokine ligand 20 [KO:K14625 ]
6366 CCL21; C-C motif chemokine ligand 21 [KO:K16062 ]
6367 CCL22; C-C motif chemokine ligand 22 [KO:K21095 ]
6369 CCL24; C-C motif chemokine ligand 24 [KO:K21097 ]
6370 CCL25; C-C motif chemokine ligand 25 [KO:K13072 ]
3579 CXCR2; C-X-C motif chemokine receptor 2 [KO:K05050 ]
3577 CXCR1; C-X-C motif chemokine receptor 1 [KO:K04175 ]
2833 CXCR3; C-X-C motif chemokine receptor 3 [KO:K04188 ]
7852 CXCR4; C-X-C motif chemokine receptor 4 [KO:K04189 ]
643 CXCR5; C-X-C motif chemokine receptor 5 [KO:K04190 ]
10663 CXCR6; C-X-C motif chemokine receptor 6 [KO:K04191 ]
2829 XCR1; X-C motif chemokine receptor 1 [KO:K04193 ]
1524 CX3CR1; C-X3-C motif chemokine receptor 1 [KO:K04192 ]
1237 CCR8; C-C motif chemokine receptor 8 [KO:K04183 ]
1235 CCR6; C-C motif chemokine receptor 6 [KO:K04181 ]
1233 CCR4; C-C motif chemokine receptor 4 [KO:K04179 ]
1236 CCR7; C-C motif chemokine receptor 7 [KO:K04182 ]
1234 CCR5; C-C motif chemokine receptor 5 [KO:K04180 ]
1230 CCR1; C-C motif chemokine receptor 1 [KO:K04176 ]
1232 CCR3; C-C motif chemokine receptor 3 [KO:K04178 ]
2826 CCR10; C-C motif chemokine receptor 10 [KO:K04185 ]
6772 STAT1; signal transducer and activator of transcription 1 [KO:K11220 ]
6773 STAT2; signal transducer and activator of transcription 2 [KO:K11221 ]
6774 STAT3; signal transducer and activator of transcription 3 [KO:K04692 ]
6777 STAT5B; signal transducer and activator of transcription 5B [KO:K11224 ]
2770 GNAI1; G protein subunit alpha i1 [KO:K04630 ]
2771 GNAI2; G protein subunit alpha i2 [KO:K04630 ]
2773 GNAI3; G protein subunit alpha i3 [KO:K04630 ]
2885 GRB2; growth factor receptor bound protein 2 [KO:K04364 ]
6654 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
6655 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
5294 PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289 ] [EC:2.7.1.153 ]
146850 PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290 ]
23533 PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290 ]
1147 CHUK; component of inhibitor of nuclear factor kappa B kinase complex [KO:K04467 ] [EC:2.7.11.10 ]
8517 IKBKG; inhibitor of nuclear factor kappa B kinase regulatory subunit gamma [KO:K07210 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
572 BAD; BCL2 associated agonist of cell death [KO:K02158 ]
10451 VAV3; vav guanine nucleotide exchange factor 3 [KO:K05730 ]
7409 VAV1; vav guanine nucleotide exchange factor 1 [KO:K05730 ]
7410 VAV2; vav guanine nucleotide exchange factor 2 [KO:K05730 ]
998 CDC42; cell division cycle 42 [KO:K04393 ]
7454 WAS; WASP actin nucleation promoting factor [KO:K05747 ]
387 RHOA; ras homolog family member A [KO:K04513 ]
2790 GNG10; G protein subunit gamma 10 [KO:K04545 ]
2791 GNG11; G protein subunit gamma 11 [KO:K04546 ]
2792 GNGT1; G protein subunit gamma transducin 1 [KO:K04548 ]
2793 GNGT2; G protein subunit gamma transducin 2 [KO:K04549 ]
57580 PREX1; phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 [KO:K12365 ]
9844 ELMO1; engulfment and cell motility 1 [KO:K12366 ]
1794 DOCK2; dedicator of cytokinesis 2 [KO:K12367 ]
9564 BCAR1; BCAR1 scaffold protein, Cas family member [KO:K05726 ]
1398 CRK; CRK proto-oncogene, adaptor protein [KO:K04438 ]
1399 CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438 ]
10235 RASGRP2; RAS guanyl releasing protein 2 [KO:K12361 ]
5906 RAP1A; RAP1A, member of RAS oncogene family [KO:K04353 ]
5908 RAP1B; RAP1B, member of RAS oncogene family [KO:K07836 ]
56288 PARD3; par-3 family cell polarity regulator [KO:K04237 ]
7074 TIAM1; TIAM Rac1 associated GEF 1 [KO:K05731 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Wong MM, Fish EN
Title
Chemokines: attractive mediators of the immune response.
Journal
Reference
Authors
Curnock AP, Logan MK, Ward SG
Title
Chemokine signalling: pivoting around multiple phosphoinositide 3-kinases.
Journal
Reference
Authors
Olson TS, Ley K
Title
Chemokines and chemokine receptors in leukocyte trafficking.
Journal
Reference
Authors
Busillo JM, Benovic JL
Title
Regulation of CXCR4 signaling.
Journal
Reference
Authors
Mellado M, Rodriguez-Frade JM, Manes S, Martinez-A C
Title
Chemokine signaling and functional responses: the role of receptor dimerization and TK pathway activation.
Journal
Reference
Authors
Knall C, Young S, Nick JA, Buhl AM, Worthen GS, Johnson GL
Title
Interleukin-8 regulation of the Ras/Raf/mitogen-activated protein kinase pathway in human neutrophils.
Journal
Reference
Authors
Patrussi L, Ulivieri C, Lucherini OM, Paccani SR, Gamberucci A, Lanfrancone L, Pelicci PG, Baldari CT
Title
p52Shc is required for CXCR4-dependent signaling and chemotaxis in T cells.
Journal
Reference
Authors
Sai J, Raman D, Liu Y, Wikswo J, Richmond A
Title
Parallel phosphatidylinositol 3-kinase (PI3K)-dependent and Src-dependent pathways lead to CXCL8-mediated Rac2 activation and chemotaxis.
Journal
Reference
Authors
Hauck CR, Klingbeil CK, Schlaepfer DD
Title
Focal adhesion kinase functions as a receptor-proximal signaling component required for directed cell migration.
Journal
Reference
Authors
Chandrasekar B, Bysani S, Mummidi S
Title
CXCL16 signals via Gi, phosphatidylinositol 3-kinase, Akt, I kappa B kinase, and nuclear factor-kappa B and induces cell-cell adhesion and aortic smooth muscle cell proliferation.
Journal
Reference
Authors
Smith L, Webb A, Ward SG
Title
T-lymphocyte navigation and migration: beyond the PI3K paradigm.
Journal
Reference
Authors
Huttenrauch F, Pollok-Kopp B, Oppermann M
Title
G protein-coupled receptor kinases promote phosphorylation and beta-arrestin-mediated internalization of CCR5 homo- and hetero-oligomers.
Journal
Reference
Authors
Thelen M, Stein JV
Title
How chemokines invite leukocytes to dance.
Journal
Reference
Authors
Ward SG, Marelli-Berg FM
Title
Mechanisms of chemokine and antigen-dependent T-lymphocyte navigation.
Journal
Reference
Authors
Schwartzberg PL, Finkelstein LD, Readinger JA
Title
TEC-family kinases: regulators of T-helper-cell differentiation.
Journal
Reference
Authors
Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL.
Title
Tec family kinases in T lymphocyte development and function.
Journal
Reference
Authors
Ticchioni M, Essafi M, Jeandel PY, Davi F, Cassuto JP, Deckert M, Bernard A
Title
Homeostatic chemokines increase survival of B-chronic lymphocytic leukemia cells through inactivation of transcription factor FOXO3a.
Journal
Reference
Authors
Korchak HM, Rossi MW, Kilpatrick LE
Title
Selective role for beta-protein kinase C in signaling for O-2 generation but not degranulation or adherence in differentiated HL60 cells.
Journal
Reference
Authors
Johnson Z, Power CA, Weiss C, Rintelen F, Ji H, Ruckle T, Camps M, Wells TN, Schwarz MK, Proudfoot AE, Rommel C
Title
Chemokine inhibition--why, when, where, which and how?
Journal
Reference
Authors
Zhelev DV, Alteraifi A
Title
Signaling in the motility responses of the human neutrophil.
Journal
Reference
Authors
Bach TL, Chen QM, Kerr WT, Wang Y, Lian L, Choi JK, Wu D, Kazanietz MG, Koretzky GA, Zigmond S, Abrams CS
Title
Phospholipase cbeta is critical for T cell chemotaxis.
Journal
Reference
Authors
Hornstein I, Alcover A, Katzav S
Title
Vav proteins, masters of the world of cytoskeleton organization.
Journal
Related pathway
hsa04060 Cytokine-cytokine receptor interaction
hsa04670 Leukocyte transendothelial migration
hsa04810 Regulation of actin cytoskeleton
KO pathway