KEGG   PATHWAY: ko04062
Entry
ko04062                     Pathway                                
Name
Chemokine signaling pathway
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
Pathway map
ko04062  Chemokine signaling pathway
ko04062

Other DBs
GO: 0070098
Orthology
K00909  GRK1_7; rhodopsin kinase [EC:2.7.11.14]
K00910  ADRBK, GRK; beta-adrenergic-receptor kinase [EC:2.7.11.15]
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01116  PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K02158  BAD; Bcl-2-antagonist of cell death
K02580  NFKB1; nuclear factor NF-kappa-B p105 subunit
K02581  NFKBIB; NF-kappa-B inhibitor beta
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02833  HRAS; GTPase HRas
K03083  GSK3B; glycogen synthase kinase 3 beta [EC:2.7.11.26]
K03099  SOS; son of sevenless
K04175  CXCR1, IL8RA, CD181; C-X-C chemokine receptor type 1
K04176  CCR1, CD191; C-C chemokine receptor type 1
K04177  CCR2, CD192; C-C chemokine receptor type 2
K04178  CCR3, CD193; C-C chemokine receptor type 3
K04179  CCR4, CD194; C-C chemokine receptor type 4
K04180  CCR5, CD195; C-C chemokine receptor type 5
K04181  CCR6, CD196; C-C chemokine receptor type 6
K04182  CCR7, CD197; C-C chemokine receptor type 7
K04183  CCR8, CDw198; C-C chemokine receptor type 8
K04184  CCR9, CDw199; C-C chemokine receptor type 9
K04185  CCR10; C-C chemokine receptor type 10
K04188  CXCR3, GPR9, CD183; C-X-C chemokine receptor type 3
K04189  CXCR4, CD184; C-X-C chemokine receptor type 4
K04190  CXCR5, BLR1, CD185; C-X-C chemokine receptor type 5
K04191  CXCR6, CD186; C-X-C chemokine receptor type 6
K04192  CX3CR1; CX3C chemokine receptor 1
K04193  XCR1; XC chemokine receptor 1
K04237  PARD3; partitioning defective protein 3
K04345  PKA; protein kinase A [EC:2.7.11.11]
K04347  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04353  RAP1A; Ras-related protein Rap-1A
K04364  GRB2; growth factor receptor-bound protein 2
K04365  BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04392  RAC1; Ras-related C3 botulinum toxin substrate 1
K04393  CDC42; cell division control protein 42
K04409  PAK1; p21-activated kinase 1 [EC:2.7.11.1]
K04438  CRK, CRKII; C-crk adapter molecule crk
K04439  ARRB; beta-arrestin
K04447  JAK2; Janus kinase 2 [EC:2.7.10.2]
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04467  IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K04513  RHOA; Ras homolog gene family, member A
K04514  ROCK1; Rho-associated protein kinase 1 [EC:2.7.11.39]
K04536  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K04538  GNB4; guanine nucleotide-binding protein subunit beta-4
K04539  GNB5; guanine nucleotide-binding protein subunit beta-5
K04540  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04547  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K04630  GNAI; guanine nucleotide-binding protein G(i) subunit alpha
K04634  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04692  STAT3; signal transducer and activator of transcription 3
K04734  NFKBIA; NF-kappa-B inhibitor alpha
K04735  RELA; transcription factor p65
K05050  CXCR2, IL8RB, CD182; C-X-C chemokine receptor type 2
K05407  PF4, CXCL4; platelet factor 4
K05408  CCL3; C-C motif chemokine 3
K05416  CXCL9; C-X-C motif chemokine 9
K05505  CXCL1_2_3, GRO; C-X-C motif chemokine 1/2/3
K05506  CXCL5_6, SCYB5_6; C-X-C motif chemokine 5/6
K05507  XCL, SCM1; C motif chemokine
K05508  CX3CL1, NTT; C-X3-C motif chemokine 1
K05509  CCL7; C-C motif chemokine 7
K05510  CCL6; C-C motif chemokine 6
K05511  CCL15_23; C-C motif chemokine 15/23
K05512  CCL19, ELC; C-C motif chemokine 19
K05513  CCL28; C-C motif chemokine 28
K05514  CCL1; C-C motif chemokine 1
K05704  SRC; tyrosine-protein kinase Src [EC:2.7.10.2]
K05725  PTK2, FAK; focal adhesion kinase 1 [EC:2.7.10.2]
K05726  BCAR1, CAS; breast cancer anti-estrogen resistance 1
K05730  VAV; guanine nucleotide exchange factor VAV
K05731  TIAM1; T-lymphoma invasion and metastasis-inducing protein 1
K05747  WAS; Wiskott-Aldrich syndrome protein
K05760  PXN; paxillin
K05854  LYN; tyrosine-protein kinase Lyn [EC:2.7.10.2]
K05858  PLCB; phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K05859  PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11]
K05871  PTK2B, FAK2; focal adhesion kinase 2 [EC:2.7.10.2]
K06068  PRKCD; novel protein kinase C delta type [EC:2.7.11.13]
K06279  SHC1; SHC-transforming protein 1
K07209  IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07363  ITK; IL2-inducible T-cell kinase [EC:2.7.10.2]
K07825  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K07826  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
K07836  RAP1B; Ras-related protein Rap-1B
K07860  RAC2; Ras-related C3 botulinum toxin substrate 2
K07861  RAC3; Ras-related C3 botulinum toxin substrate 3
K08011  NCF1, P47PHOX; neutrophil cytosolic factor 1
K08041  ADCY1; adenylate cyclase 1 [EC:4.6.1.1]
K08042  ADCY2; adenylate cyclase 2 [EC:4.6.1.1]
K08043  ADCY3; adenylate cyclase 3 [EC:4.6.1.1]
K08044  ADCY4; adenylate cyclase 4 [EC:4.6.1.1]
K08045  ADCY5; adenylate cyclase 5 [EC:4.6.1.1]
K08046  ADCY6; adenylate cyclase 6 [EC:4.6.1.1]
K08047  ADCY7; adenylate cyclase 7 [EC:4.6.1.1]
K08048  ADCY8; adenylate cyclase 8 [EC:4.6.1.1]
K08049  ADCY9; adenylate cyclase 9 [EC:4.6.1.1]
K08291  GRK4_5_6; G protein-coupled receptor kinase [EC:2.7.11.16]
K08822  GSK3A; glycogen synthase kinase 3 alpha [EC:2.7.11.26]
K08891  FGR, SRC2; tyrosine-protein kinase Fgr [EC:2.7.10.2]
K08893  HCK; hemopoietic cell kinase [EC:2.7.10.2]
K09408  FOXO3; forkhead box protein O3
K10029  PPBP, CXCL7; platelet basic protein
K10030  IL8, CXCL8; interleukin 8
K10031  CXCL12; C-X-C motif chemokine 12
K10032  CXCL13; C-X-C motif chemokine 13
K10033  CXCL14, SCYB14; C-X-C motif chemokine 14
K10034  CXCL15; C-X-C motif chemokine 15
K10035  CXCL16; C-X-C motif chemokine 16
K11218  JAK3; Janus kinase 3 [EC:2.7.10.2]
K11220  STAT1; signal transducer and activator of transcription 1
K11221  STAT2; signal transducer and activator of transcription 2
K11224  STAT5B; signal transducer and activator of transcription 5B
K12361  RASGRP2; RAS guanyl-releasing protein 2
K12365  PREX1; phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchanger 1 protein
K12366  ELMO1, CED12; engulfment and cell motility protein 1
K12367  DOCK2; dedicator of cytokinesis protein 2
K12499  CCL5; C-C motif chemokine 5
K12671  CXCL10, IP10; C-X-C motif chemokine 10
K12672  CXCL11, I-TAC; C-X-C motif chemokine 11
K12964  CCL4; C-C motif chemokine 4
K13072  CCL25; C-C motif chemokine 25
K14624  CCL2, MCP1; C-C motif chemokine 2
K14625  CCL20; C-C motif chemokine 20
K16062  CCL21, SLC; C-C motif chemokine 21
K16595  CCL13; C-C motif chemokine 13
K16596  CCL8; C-C motif chemokine 8
K16597  CCL11; C-C motif chemokine 11
K16598  CCL27; C-C motif chemokine 27
K17388  ROCK2; Rho-associated protein kinase 2 [EC:2.7.11.39]
K17447  SHC2; SHC-transforming protein 2
K17448  SHC3; SHC-transforming protein 3
K17449  SHC4; SHC-transforming protein 4
K18952  PRKCZ; atypical protein kinase C zeta type [EC:2.7.11.13]
K19662  PRKCB; classical protein kinase C beta type [EC:2.7.11.13]
K21083  CCL17; C-C motif chemokine 17
K21092  CCL14; C-C motif chemokine 14
K21093  CCL16; C-C motif chemokine 16
K21094  CCL18; C-C motif chemokine 18
K21095  CCL22; C-C motif chemokine 22
K21096  CCL26; C-C motif chemokine 26
K21097  CCL24; C-C motif chemokine 24
K21289  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [EC:2.7.1.153]
K21290  PIK3R5_6; phosphoinositide-3-kinase regulatory subunit 5/6
K22671  CCL9; C-C motif chemokine 9
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:12495636
  Authors
Wong MM, Fish EN
  Title
Chemokines: attractive mediators of the immune response.
  Journal
Semin Immunol 15:5-14 (2003)
DOI:10.1016/S1044-5323(02)00123-9
Reference
PMID:11872087
  Authors
Curnock AP, Logan MK, Ward SG
  Title
Chemokine signalling: pivoting around multiple phosphoinositide 3-kinases.
  Journal
Immunology 105:125-36 (2002)
DOI:10.1046/j.1365-2567.2002.01345.x
Reference
PMID:12069927
  Authors
Olson TS, Ley K
  Title
Chemokines and chemokine receptors in leukocyte trafficking.
  Journal
Am J Physiol Regul Integr Comp Physiol 283:R7-28 (2002)
DOI:10.1152/ajpregu.00738.2001
Reference
PMID:17169327
  Authors
Busillo JM, Benovic JL
  Title
Regulation of CXCR4 signaling.
  Journal
Biochim Biophys Acta 1768:952-63 (2007)
DOI:10.1016/j.bbamem.2006.11.002
Reference
PMID:11244042
  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
Annu Rev Immunol 19:397-421 (2001)
DOI:10.1146/annurev.immunol.19.1.397
Reference
PMID:8576262
  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
J Biol Chem 271:2832-8 (1996)
DOI:10.1074/jbc.271.5.2832
Reference
PMID:17537990
  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
Blood 110:1730-8 (2007)
DOI:10.1182/blood-2007-01-068411
Reference
PMID:18662984
  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
J Biol Chem 283:26538-47 (2008)
DOI:10.1074/jbc.M805611200
Reference
PMID:10852130
  Authors
Hauck CR, Klingbeil CK, Schlaepfer DD
  Title
Focal adhesion kinase functions as a receptor-proximal signaling component required for directed cell migration.
  Journal
Immunol Res 21:293-303 (2000)
DOI:10.1385/IR:21:2-3:293
Reference
PMID:14625285
  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
J Biol Chem 279:3188-96 (2004)
DOI:10.1074/jbc.M311660200
Reference
PMID:17371236
  Authors
Smith L, Webb A, Ward SG
  Title
T-lymphocyte navigation and migration: beyond the PI3K paradigm.
  Journal
Biochem Soc Trans 35:193-8 (2007)
DOI:10.1042/BST0350193
Reference
PMID:16144840
  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
J Biol Chem 280:37503-15 (2005)
DOI:10.1074/jbc.M500535200
Reference
PMID:18711432
  Authors
Thelen M, Stein JV
  Title
How chemokines invite leukocytes to dance.
  Journal
Nat Immunol 9:953-9 (2008)
DOI:10.1038/ni.f.207
Reference
PMID:19159344
  Authors
Ward SG, Marelli-Berg FM
  Title
Mechanisms of chemokine and antigen-dependent T-lymphocyte navigation.
  Journal
Biochem J 418:13-27 (2009)
DOI:10.1042/BJ20081969
Reference
PMID:15803148
  Authors
Schwartzberg PL, Finkelstein LD, Readinger JA
  Title
TEC-family kinases: regulators of T-helper-cell differentiation.
  Journal
Nat Rev Immunol 5:284-95 (2005)
DOI:10.1038/nri1591
Reference
PMID:15771581
  Authors
Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL.
  Title
Tec family kinases in T lymphocyte development and function.
  Journal
Annu Rev Immunol 23:549-600 (2005)
DOI:10.1146/annurev.immunol.22.012703.104743
Reference
PMID:17496928
  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
Oncogene 26:7081-91 (2007)
DOI:10.1038/sj.onc.1210519
Reference
PMID:9765254
  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
J Biol Chem 273:27292-9 (1998)
DOI:10.1074/jbc.273.42.27292
Reference
PMID:15046611
  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
Biochem Soc Trans 32:366-77 (2004)
DOI:10.1042/bst0320366
Reference
PMID:12051620
  Authors
Zhelev DV, Alteraifi A
  Title
Signaling in the motility responses of the human neutrophil.
  Journal
Ann Biomed Eng 30:356-70 (2002)
DOI:10.1114/1.1477446
Reference
PMID:17675482
  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
J Immunol 179:2223-7 (2007)
DOI:10.4049/jimmunol.179.4.2223
Reference
PMID:14607270
  Authors
Hornstein I, Alcover A, Katzav S
  Title
Vav proteins, masters of the world of cytoskeleton organization.
  Journal
Cell Signal 16:1-11 (2004)
DOI:10.1016/S0898-6568(03)00110-4
Related
pathway
ko04010  MAPK signaling pathway
ko04060  Cytokine-cytokine receptor interaction
ko04120  Ubiquitin mediated proteolysis
ko04630  JAK-STAT signaling pathway
ko04670  Leukocyte transendothelial migration
ko04810  Regulation of actin cytoskeleton

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