KEGG   PATHWAY: tup04062
Entry
tup04062                    Pathway                                
Name
Chemokine signaling pathway - Tupaia chinensis (Chinese tree shrew)
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
tup04062  Chemokine signaling pathway
tup04062

Other DBs
GO: 0070098
Organism
Tupaia chinensis (Chinese tree shrew) [GN:tup]
Gene
102467686  [KO:K05505]
102467864  VAV2; vav guanine nucleotide exchange factor 2 [KO:K05730]
102467951  [KO:K04542]
102467954  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102468263  GNAQ; G protein subunit alpha q [KO:K04634]
102468347  [KO:K04182]
102468478  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102468592  RASGRP2; RAS guanyl releasing protein 2 [KO:K12361]
102468763  CCR7; C-C chemokine receptor type 7 [KO:K04182]
102468873  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
102468910  CCL7; C-C motif chemokine 7 [KO:K05509]
102469016  CCL28; C-C motif chemokine ligand 28 [KO:K05513]
102469132  WAS; Wiskott-Aldrich syndrome [KO:K05747]
102469271  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102469401  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102469651  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
102470181  CCL11; eotaxin [KO:K16597]
102470314  CCR9; C-C motif chemokine receptor 9 [KO:K04184]
102470324  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
102471344  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
102471949  JAK3; Janus kinase 3 [KO:K11218] [EC:2.7.10.2]
102472005  CXCR4; C-X-C motif chemokine receptor 4 [KO:K04189]
102472172  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102472239  DOCK2; dedicator of cytokinesis 2 [KO:K12367]
102472295  SHC3; SHC adaptor protein 3 [KO:K17448]
102472317  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
102472381  RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
102472442  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
102472532  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102472622  [KO:K05505]
102473006  [KO:K05509]
102473093  XCL1; X-C motif chemokine ligand 1 [KO:K05507]
102473341  PPBP; pro-platelet basic protein [KO:K10029]
102473754  PF4; platelet factor 4 [KO:K05407]
102473837  CCL1; C-C motif chemokine ligand 1 [KO:K05514]
102474297  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102474598  GRK6; G protein-coupled receptor kinase 6 [KO:K08291] [EC:2.7.11.16]
102475072  RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
102475088  CXCL14; C-X-C motif chemokine ligand 14 [KO:K10033]
102475420  GNAI2; G protein subunit alpha i2 [KO:K04630]
102475940  CCL25; C-C motif chemokine ligand 25 [KO:K13072]
102476038  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
102476196  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102476261  GSK3A; glycogen synthase kinase 3 alpha [KO:K08822] [EC:2.7.11.26]
102476496  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102476590  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
102476704  GNG13; G protein subunit gamma 13 [KO:K04547]
102476737  GNAI3; G protein subunit alpha i3 [KO:K04630]
102476758  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
102476928  GNG7; G protein subunit gamma 7 [KO:K04543]
102477222  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
102477344  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
102477389  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
102477438  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102477532  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
102477989  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
102478525  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102478768  CCL4; C-C motif chemokine 4 [KO:K12964]
102479102  RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
102479188  CCL3; C-C motif chemokine 3 [KO:K05408]
102479323  GNAI1; G protein subunit alpha i1 [KO:K04630]
102479597  CCL15; C-C motif chemokine 15 [KO:K05511]
102479628  FOXO3; forkhead box O3 [KO:K09408]
102479734  SHC4; SHC adaptor protein 4 [KO:K17449]
102480022  CCL14; C-C motif chemokine ligand 14 [KO:K21092]
102480420  GRK4; G protein-coupled receptor kinase 4 [KO:K08291] [EC:2.7.11.16]
102480437  CCL16; C-C motif chemokine ligand 16 [KO:K21093]
102480904  CXCR3; C-X-C motif chemokine receptor 3 [KO:K04188]
102481002  SHC1; SHC adaptor protein 1 [KO:K06279]
102481136  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.39]
102481282  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
102481841  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
102481863  SHC2; SHC adaptor protein 2 [KO:K17447]
102482004  GRK2; G protein-coupled receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
102482352  GNB1; G protein subunit beta 1 [KO:K04536]
102482865  CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438]
102483057  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102483329  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102483369  PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
102483786  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
102484212  GNB2; G protein subunit beta 2 [KO:K04537]
102484248  CXCL9; C-X-C motif chemokine ligand 9 [KO:K05416]
102484375  CXCR1; C-X-C motif chemokine receptor 1 [KO:K04175]
102484444  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102484500  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102484805  CXCR2; C-X-C motif chemokine receptor 2 [KO:K05050]
102485065  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
102485563  CCL22; C-C motif chemokine ligand 22 [KO:K21095]
102485614  VAV1; vav guanine nucleotide exchange factor 1 [KO:K05730]
102485949  CCL20; C-C motif chemokine ligand 20 [KO:K14625]
102485965  GRK5; G protein-coupled receptor kinase 5 [KO:K08291] [EC:2.7.11.16]
102486599  CRK; CRK proto-oncogene, adaptor protein [KO:K04438]
102487039  RHOA; ras homolog family member A [KO:K04513]
102487091  GRK7; G protein-coupled receptor kinase 7 [KO:K00909] [EC:2.7.11.14]
102487413  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102487568  GNB5; G protein subunit beta 5 [KO:K04539]
102487574  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
102487894  CXCL11; C-X-C motif chemokine ligand 11 [KO:K12672]
102488035  ELMO1; engulfment and cell motility 1 [KO:K12366]
102488324  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
102488344  CDC42; cell division cycle 42 [KO:K04393]
102488378  VAV3; vav guanine nucleotide exchange factor 3 [KO:K05730]
102488824  BCAR1; BCAR1, Cas family scaffolding protein [KO:K05726]
102489750  ITK; IL2 inducible T-cell kinase [KO:K07363] [EC:2.7.10.2]
102490242  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.39]
102490273  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
102490451  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102490639  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
102490695  GNG2; G protein subunit gamma 2 [KO:K07826]
102491217  ARRB1; arrestin beta 1 [KO:K04439]
102491330  HCK; HCK proto-oncogene, Src family tyrosine kinase [KO:K08893] [EC:2.7.10.2]
102491807  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
102491914  GNGT1; G protein subunit gamma transducin 1 [KO:K04548]
102492323  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
102492339  GNG11; G protein subunit gamma 11 [KO:K04546]
102492353  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
102492507  CCR8; C-C motif chemokine receptor 8 [KO:K04183]
102492738  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
102492771  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102492903  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102493080  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102493204  CX3CR1; C-X3-C motif chemokine receptor 1 [KO:K04192]
102493230  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102493456  PARD3; par-3 family cell polarity regulator [KO:K04237]
102493585  LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
102493758  GNG4; G protein subunit gamma 4 [KO:K04541]
102493874  GNG8; G protein subunit gamma 8 [KO:K04544]
102494629  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
102494635  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102494727  RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
102494811  CCL26; C-C motif chemokine ligand 26 [KO:K21096]
102494820  GNG3; G protein subunit gamma 3 [KO:K04540]
102495211  CCL24; C-C motif chemokine ligand 24 [KO:K21097]
102495416  CX3CL1; C-X3-C motif chemokine ligand 1 [KO:K05508]
102495430  PAK1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
102495436  RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
102495706  GNGT2; G protein subunit gamma transducin 2 [KO:K04549]
102495836  CCL17; C-C motif chemokine ligand 17 [KO:K21083]
102496453  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102496534  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102496578  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
102496631  [KO:K16598]
102496652  NFKBIB; NFKB inhibitor beta [KO:K02581]
102497124  ARRB2; arrestin beta 2 [KO:K04439]
102497480  CCL27; C-C motif chemokine ligand 27 [KO:K16598]
102497488  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102497549  CXCL16; C-X-C motif chemokine ligand 16 [KO:K10035]
102497978  XCR1; X-C motif chemokine receptor 1 [KO:K04193]
102498069  BAD; BCL2 associated agonist of cell death [KO:K02158]
102498148  CCL19; C-C motif chemokine ligand 19 [KO:K05512]
102498372  CCR1; C-C motif chemokine receptor 1 [KO:K04176]
102498554  CCL21; C-C motif chemokine ligand 21 [KO:K16062]
102498785  CCR3; C-C motif chemokine receptor 3 [KO:K04178]
102498944  CCR10; C-C motif chemokine receptor 10 [KO:K04185]
102499203  CCR5; C-C chemokine receptor type 5 [KO:K04180]
102499209  FGR; FGR proto-oncogene, Src family tyrosine kinase [KO:K08891] [EC:2.7.10.2]
102499442  GRK3; G protein-coupled receptor kinase 3 [KO:K00910] [EC:2.7.11.15]
102499461  PXN; paxillin [KO:K05760]
102499629  CCR2; C-C motif chemokine receptor 2 [KO:K04177]
102499711  CXCL12; C-X-C motif chemokine ligand 12 [KO:K10031]
102500069  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102500530  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102500733  TIAM1; T-cell lymphoma invasion and metastasis 1 [KO:K05731]
102501308  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
102501352  CCR6; C-C motif chemokine receptor 6 [KO:K04181]
102501535  GNG12; G protein subunit gamma 12 [KO:K04347]
102502106  JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
102502163  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102502175  [KO:K05506]
102502248  CXCL13; C-X-C motif chemokine ligand 13 [KO:K10032]
102502283  NCF1; neutrophil cytosolic factor 1 [KO:K08011]
102502506  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
102502817  CXCR5; C-X-C motif chemokine receptor 5 [KO:K04190]
102503265  GNB3; G protein subunit beta 3 [KO:K07825]
102503289  CCR4; C-C motif chemokine receptor 4 [KO:K04179]
102503329  PRKCZ; protein kinase C zeta [KO:K18952] [EC:2.7.11.13]
106734070  CXCR6; C-X-C motif chemokine receptor 6 [KO:K04191]
106736453  [KO:K00922] [EC:2.7.1.153]
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
tup04010  MAPK signaling pathway
tup04060  Cytokine-cytokine receptor interaction
tup04120  Ubiquitin mediated proteolysis
tup04630  JAK-STAT signaling pathway
tup04670  Leukocyte transendothelial migration
tup04810  Regulation of actin cytoskeleton
KO pathway
ko04062   

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