KEGG   PATHWAY: bacu04062
Entry
bacu04062                   Pathway                                
Name
Chemokine signaling pathway - Balaenoptera acutorostrata scammoni (minke whale)
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
bacu04062  Chemokine signaling pathway
bacu04062

Other DBs
GO: 0070098
Organism
Balaenoptera acutorostrata scammoni (minke whale) [GN:bacu]
Gene
103005635  growth-regulated protein homolog alpha-like [KO:K05505]
103006206  growth-regulated protein homolog alpha-like [KO:K05505]
103005920  growth-regulated protein homolog alpha-like [KO:K05505]
103010959  CXCL6; C-X-C motif chemokine ligand 6 [KO:K05506]
103010680  PPBP; pro-platelet basic protein [KO:K10029]
103006782  CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030]
103000390  CXCL9; C-X-C motif chemokine ligand 9 [KO:K05416]
103000674  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
103019414  CXCL11; C-X-C motif chemokine ligand 11 [KO:K12672]
103011229  CXCL12; C-X-C motif chemokine ligand 12 [KO:K10031]
103015873  c-X-C motif chemokine 13-like [KO:K10032]
103020809  CXCL13; C-X-C motif chemokine ligand 13 [KO:K10032]
103006707  CXCL16; C-X-C motif chemokine ligand 16 [KO:K10035]
103006487  PF4; platelet factor 4 [KO:K05407]
103003366  CXCL14; C-X-C motif chemokine ligand 14 [KO:K10033]
103007438  lymphotactin-like [KO:K05507]
103007128  lymphotactin-like [KO:K05507]
103004825  CX3CL1; C-X3-C motif chemokine ligand 1 [KO:K05508]
103013593  CCL1; C-C motif chemokine ligand 1 [KO:K05514]
103014608  CCL2; C-C motif chemokine ligand 2 [KO:K14624]
103001344  c-C motif chemokine 3-like [KO:K05408]
103001880  c-C motif chemokine 3-like [KO:K05408]
103001618  CCL4; C-C motif chemokine ligand 4 [KO:K12964]
102999955  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
103015160  CCL8; C-C motif chemokine ligand 8 [KO:K16596]
103014886  CCL11; C-C motif chemokine ligand 11 [KO:K16597]
103000784  CCL14; C-C motif chemokine ligand 14 [KO:K21092]
103001061  CCL23; C-C motif chemokine ligand 23 [KO:K05511]
103000496  CCL16; C-C motif chemokine ligand 16 [KO:K21093]
103004541  CCL17; C-C motif chemokine ligand 17 [KO:K21083]
103012584  CCL19; C-C motif chemokine ligand 19 [KO:K05512]
103006233  CCL20; C-C motif chemokine ligand 20 [KO:K14625]
103018667  CCL21; C-C motif chemokine ligand 21 [KO:K16062]
103005112  CCL22; C-C motif chemokine ligand 22 [KO:K21095]
103007099  CCL24; C-C motif chemokine ligand 24 [KO:K21097]
103008296  CCL25; C-C motif chemokine ligand 25 [KO:K13072]
103011918  uncharacterized LOC103011918 [KO:K05513]
103020356  CXCR2; C-X-C motif chemokine receptor 2 [KO:K05050]
103014593  c-X-C chemokine receptor type 2-like [KO:K04175]
102997528  CXCR3; C-X-C motif chemokine receptor 3 [KO:K04188]
103004476  CXCR4; C-X-C motif chemokine receptor 4 [KO:K04189]
103011721  CXCR5; C-X-C motif chemokine receptor 5 [KO:K04190]
103004742  XCR1; X-C motif chemokine receptor 1 [KO:K04193]
103004942  CX3CR1; C-X3-C motif chemokine receptor 1 [KO:K04192]
103004648  CCR8; C-C motif chemokine receptor 8 [KO:K04183]
103000473  CCR6; C-C motif chemokine receptor 6 [KO:K04181]
103006045  CCR9; C-C motif chemokine receptor 9 [KO:K04184]
103016565  CCR4; C-C motif chemokine receptor 4 [KO:K04179]
103011340  CCR7; C-C motif chemokine receptor 7 [KO:K04182]
103003157  CCR2; C-C motif chemokine receptor 2 [KO:K04177]
103002871  CCR5; C-C motif chemokine receptor 5 [KO:K04180]
103004076  CCR1; C-C motif chemokine receptor 1 [KO:K04176]
103003637  CCR3; C-C motif chemokine receptor 3 [KO:K04178]
103020501  CCR10; chemokine (C-C motif) receptor 10 [KO:K04185]
103016904  JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
103012385  JAK3; Janus kinase 3 [KO:K11218] [EC:2.7.10.2]
103013781  signal transducer and activator of transcription 1-like [KO:K11220]
103000458  STAT2; signal transducer and activator of transcription 2 [KO:K11221]
102997405  signal transducer and activator of transcription 3-like [KO:K04692]
103008157  STAT3; signal transducer and activator of transcription 3 (acute-phase response factor) [KO:K04692]
103017385  GNAI1; G protein subunit alpha i1 [KO:K04630]
103010531  GNAI2; G protein subunit alpha i2 [KO:K04630]
103008589  GNAI3; G protein subunit alpha i3 [KO:K04630]
102998650  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
103020085  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
103020845  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
103005549  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
103006764  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
103014094  ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
102997912  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
103019172  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
103016058  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
103000011  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
103008319  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103001606  LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
103015546  HCK; HCK proto-oncogene, Src family tyrosine kinase [KO:K08893] [EC:2.7.10.2]
103016939  FGR; FGR proto-oncogene, Src family tyrosine kinase [KO:K08891] [EC:2.7.10.2]
103001801  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
103015382  SHC1; SHC adaptor protein 1 [KO:K06279]
103006868  SHC2; SHC adaptor protein 2 [KO:K17447]
103017986  SHC3; SHC adaptor protein 3 [KO:K17448]
102999132  SHC4; SHC adaptor protein 4 [KO:K17449]
103010512  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102999196  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103019365  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103006545  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
103015457  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
103004931  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103014337  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103002372  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
103017381  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102999619  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103002590  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103012691  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103012931  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103014043  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103008077  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103009307  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103007464  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103004888  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
103014949  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
103015229  PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290]
103004909  PRKCZ; protein kinase C zeta [KO:K18952] [EC:2.7.11.13]
103002026  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103013147  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103004139  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102999779  FOXO3; forkhead box O3 [KO:K09408]
103015414  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
103015119  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103017855  NF-kappa-B essential modulator-like [KO:K07210]
103002206  NFKBIA; NFKB inhibitor alpha [KO:K04734]
103006581  NFKBIB; NFKB inhibitor beta [KO:K02581]
102999230  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
103019614  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
103005702  BAD; BCL2 associated agonist of cell death [KO:K02158]
103016833  GSK3A; glycogen synthase kinase 3 alpha [KO:K08822] [EC:2.7.11.26]
102998893  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
103010220  ITK; IL2 inducible T-cell kinase [KO:K07363] [EC:2.7.10.2]
103002083  VAV2; vav guanine nucleotide exchange factor 2 [KO:K05730]
103018979  VAV1; vav guanine nucleotide exchange factor 1 [KO:K05730]
103019070  VAV3; vav guanine nucleotide exchange factor 3 [KO:K05730]
103007995  RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
103006132  RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
103019253  RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
103010714  PAK1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
103008817  CDC42; cell division cycle 42 [KO:K04393]
103013907  WAS; Wiskott-Aldrich syndrome [KO:K05747]
103019793  RHOA; ras homolog family member A [KO:K04513]
103002971  rho-associated protein kinase 1-like [KO:K04514] [EC:2.7.11.1]
102999355  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
103006513  GNB1; G protein subunit beta 1 [KO:K04536]
103000308  GNB2; G protein subunit beta 2 [KO:K04537]
103008105  GNB3; G protein subunit beta 3 [KO:K07825]
103001811  GNB4; G protein subunit beta 4 [KO:K04538]
103000160  GNB5; G protein subunit beta 5 [KO:K04539]
103004854  GNG2; G protein subunit gamma 2 [KO:K07826]
103019275  GNG4; G protein subunit gamma 4 [KO:K04541]
103017244  GNG7; G protein subunit gamma 7 [KO:K04543]
102997635  GNG8; G protein subunit gamma 8 [KO:K04544]
103007358  GNG11; G protein subunit gamma 11 [KO:K04546]
103016707  GNG13; G protein subunit gamma 13 [KO:K04547]
103007657  GNGT1; G protein subunit gamma transducin 1 [KO:K04548]
103007192  PREX1; phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 [KO:K12365]
103015274  ELMO1; engulfment and cell motility 1 [KO:K12366]
103011592  DOCK2; dedicator of cytokinesis 2 [KO:K12367]
103013388  PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
103003171  PXN; paxillin [KO:K05760]
102999909  BCAR1; breast cancer anti-estrogen resistance 1 [KO:K05726]
103020871  CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438]
103001411  CRK; CRK proto-oncogene, adaptor protein [KO:K04438]
103016023  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
103018216  GNAQ; G protein subunit alpha q [KO:K04634]
103020805  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102997432  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
103007077  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
103006361  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
103016663  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
103014764  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
103000066  RASGRP2; RAS guanyl releasing protein 2 [KO:K12361]
103017880  RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
103019004  RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
103018737  ras-related protein Rap-1b-like [KO:K07836]
103004935  PARD3; par-3 family cell polarity regulator [KO:K04237]
103016623  TIAM1; T-cell lymphoma invasion and metastasis 1 [KO:K05731]
103012542  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
103000809  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
103021081  neutrophil cytosol factor 1-like [KO:K08011]
103013851  GRK7; G protein-coupled receptor kinase 7 [KO:K00909] [EC:2.7.11.14]
103002736  GRK1; G protein-coupled receptor kinase 1 [KO:K00909] [EC:2.7.11.14]
103005732  GRK3; G protein-coupled receptor kinase 3 [KO:K00910] [EC:2.7.11.15]
103019615  GRK2; G protein-coupled receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
103017883  GRK6; G protein-coupled receptor kinase 6 [KO:K08291] [EC:2.7.11.16]
103011898  GRK4; G protein-coupled receptor kinase 4 [KO:K08291] [EC:2.7.11.16]
103005786  GRK5; G protein-coupled receptor kinase 5 [KO:K08291] [EC:2.7.11.16]
103021082  ARRB2; arrestin beta 2 [KO:K04439]
103017343  ARRB1; arrestin beta 1 [KO:K04439]
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
bacu04010  MAPK signaling pathway
bacu04060  Cytokine-cytokine receptor interaction
bacu04120  Ubiquitin mediated proteolysis
bacu04630  JAK-STAT signaling pathway
bacu04670  Leukocyte transendothelial migration
bacu04810  Regulation of actin cytoskeleton
KO pathway
ko04062   
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