KEGG   PATHWAY: mdo04062
Entry
mdo04062                    Pathway                                
Name
Chemokine signaling pathway - Monodelphis domestica (gray short-tailed opossum)
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
mdo04062  Chemokine signaling pathway
mdo04062

Other DBs
GO: 0070098
Organism
Monodelphis domestica (gray short-tailed opossum) [GN:mdo]
Gene
100009767  [KO:K04393]
100009844  GRK3; G protein-coupled receptor kinase 3 [KO:K00910] [EC:2.7.11.15]
100009879  PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K21289] [EC:2.7.1.153]
100010184  [KO:K04347]
100010412  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
100010452  GNG3; G protein subunit gamma 3 [KO:K04540]
100010539  HCK; HCK proto-oncogene, Src family tyrosine kinase [KO:K08893] [EC:2.7.10.2]
100010720  JAK3; Janus kinase 3 [KO:K11218] [EC:2.7.10.2]
100010736  GNB1; G protein subunit beta 1 [KO:K04536]
100011015  GNG5; G protein subunit gamma 5 [KO:K04542]
100011211  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
100011382  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
100011470  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
100011497  CCR10; C-C motif chemokine receptor 10 [KO:K04185]
100011605  GNAQ; G protein subunit alpha q [KO:K04634]
100011769  NFKBIA; NFKB inhibitor alpha [KO:K04734]
100012179  ARRB1; arrestin beta 1 [KO:K04439]
100012266  CXCR1; C-X-C chemokine receptor type 1 [KO:K04175]
100012302  CXCR2; C-X-C chemokine receptor type 2 [KO:K05050]
100012317  CRK; CRK proto-oncogene, adaptor protein [KO:K04438]
100012447  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
100012464  PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290]
100012916  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100013032  CXCR3; C-X-C motif chemokine receptor 3 [KO:K04188]
100013052  GNAI1; G protein subunit alpha i1 [KO:K04630]
100013164  ADCY2; adenylate cyclase 2 [KO:K08042] [EC:4.6.1.1]
100013346  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
100013546  GNB4; G protein subunit beta 4 [KO:K04538]
100013691  NFKBIB; NFKB inhibitor beta [KO:K02581]
100013759  GNB3; G protein subunit beta 3 [KO:K07825]
100013800  GRK7; G protein-coupled receptor kinase 7 [KO:K00909] [EC:2.7.11.14]
100013823  ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
100013831  ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
100014077  CXCL14; C-X-C motif chemokine ligand 14 [KO:K10033]
100014092  RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
100014144  NCF1; neutrophil cytosolic factor 1 [KO:K08011]
100014446  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
100014564  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
100014687  GNG7; G protein subunit gamma 7 [KO:K04543]
100014847  [KO:K04439]
100015064  TIAM1; T-cell lymphoma invasion and metastasis 1 [KO:K05731]
100015312  CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438]
100015350  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
100015410  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
100015808  CCR7; C-C motif chemokine receptor 7 [KO:K04182]
100016052  ARRB2; arrestin beta 2 [KO:K04439]
100016090  SHC1; SHC adaptor protein 1 [KO:K06279]
100016174  GRK1; G protein-coupled receptor kinase 1 [KO:K00909] [EC:2.7.11.14]
100016207  CXCL12; C-X-C motif chemokine ligand 12 [KO:K10031]
100016627  CXCR4; C-X-C motif chemokine receptor 4 [KO:K04189]
100016914  GNG12; G protein subunit gamma 12 [KO:K04347]
100016961  GNG8; G protein subunit gamma 8 [KO:K04544]
100017094  CCL28; C-C motif chemokine ligand 28 [KO:K05513]
100017283  [KO:K12964]
100017328  [KO:K12964]
100017332  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
100017364  [KO:K12964]
100017392  GNB2; G protein subunit beta 2 [KO:K04537]
100017393  [KO:K12964]
100017436  [KO:K12964]
100017439  GNG13; G protein subunit gamma 13 [KO:K04547]
100017517  RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
100017930  JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
100018189  GNG10; G protein subunit gamma 10 [KO:K04545]
100018336  PAK1; p21 (RAC1) activated kinase 1 [KO:K04409] [EC:2.7.11.1]
100018410  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100018699  WAS; Wiskott-Aldrich syndrome [KO:K05747]
100018838  GNGT2; G protein subunit gamma transducin 2 [KO:K04549]
100018887  [KO:K05507]
100018972  [KO:K04188]
100019274  ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
100019317  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
100019947  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
100020001  [KO:K18952] [EC:2.7.11.13]
100020150  VAV1; vav guanine nucleotide exchange factor 1 [KO:K05730]
100020306  [KO:K18952] [EC:2.7.11.13]
100020842  [KO:K12964]
100021011  CCL5; C-C motif chemokine ligand 5 [KO:K12499]
100021110  RHOA; ras homolog family member A [KO:K04513]
100021132  GNG4; G protein subunit gamma 4 [KO:K04541]
100021210  CCL20; C-C motif chemokine ligand 20 [KO:K14625]
100021366  GRK4; G protein-coupled receptor kinase 4 [KO:K08291] [EC:2.7.11.16]
100021382  CCL22; C-C motif chemokine ligand 22 [KO:K21095]
100021471  CCL17; C-C motif chemokine 17 [KO:K21083]
100021705  FOXO3; forkhead box O3 [KO:K09408]
100022317  [KO:K05408]
100022523  [KO:K07828]
100022889  PARD3; par-3 family cell polarity regulator [KO:K04237]
100022894  GRB2; growth factor receptor bound protein 2 [KO:K04364]
100022918  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
100022975  ELMO1; engulfment and cell motility 1 [KO:K12366]
100023099  CDC42; cell division cycle 42 [KO:K04393]
100023438  [KO:K04180]
100023722  IL8; interleukin-8 [KO:K10030]
100023783  CXCL1; growth-regulated alpha protein [KO:K05505]
100024057  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
100024494  PXN; paxillin [KO:K05760]
100024603  SHC3; SHC adaptor protein 3 [KO:K17448]
100024769  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
100025175  PTK2B; protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
100025332  ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
100025996  CXCL11; C-X-C motif chemokine ligand 11 [KO:K12672]
100026232  GRK5; G protein-coupled receptor kinase 5 [KO:K08291] [EC:2.7.11.16]
100026554  ADCY8; adenylate cyclase 8 [KO:K08048] [EC:4.6.1.1]
100026861  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100026992  RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
100027188  PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
100027373  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
100027579  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
100027952  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
100028096  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100028636  CCR4; C-C motif chemokine receptor 4 [KO:K04179]
100028655  CX3CR1; C-X3-C motif chemokine receptor 1 [KO:K04192]
100028671  [KO:K04183]
100028687  [KO:K04183]
100028728  CCL21; C-C motif chemokine ligand 21 [KO:K16062]
100028745  CCL19; C-C motif chemokine ligand 19 [KO:K05512]
100028763  CCL27; C-C motif chemokine ligand 27 [KO:K16598]
100028917  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
100029256  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
100029391  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
100029404  PREX1; phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 [KO:K12365]
100029731  [KO:K04180]
100029844  VAV3; vav guanine nucleotide exchange factor 3 [KO:K05730]
100029873  RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
100029937  CCR9; C-C motif chemokine receptor 9 [KO:K04184]
100029955  XCR1; X-C motif chemokine receptor 1 [KO:K04193]
100029967  CCR1; C-C chemokine receptor type 1 [KO:K04176]
100029988  CCR3; C-C chemokine receptor type 3 [KO:K04178]
100030002  [KO:K04180]
100030005  ITK; IL2 inducible T-cell kinase [KO:K07363] [EC:2.7.10.2]
100030053  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
100030095  GNAI3; G protein subunit alpha i3 [KO:K04630]
100030202  PRKCZ; protein kinase C zeta [KO:K18952] [EC:2.7.11.13]
100030463  ADCY1; adenylate cyclase 1 [KO:K08041] [EC:4.6.1.1]
100030722  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
100030872  ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
100030952  DOCK2; dedicator of cytokinesis 2 [KO:K12367]
100031128  SHC4; SHC adaptor protein 4 [KO:K17449]
100031246  BAD; BCL2 associated agonist of cell death [KO:K02158]
100031263  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
100031379  CXCR5; C-X-C motif chemokine receptor 5 [KO:K04190]
100031383  GNB5; G protein subunit beta 5 [KO:K04539]
100031660  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
100031869  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
100031943  GRK6; G protein-coupled receptor kinase 6 [KO:K08291] [EC:2.7.11.16]
100032298  [KO:K04345] [EC:2.7.11.11]
100032608  CCR6; C-C motif chemokine receptor 6 [KO:K04181]
100032696  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
100032706  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.39]
100032726  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
100032921  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
100032986  GNAI2; G protein subunit alpha i2 [KO:K04630]
100033031  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100033128  RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
100033281  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
100616821  LYN; LYN proto-oncogene, Src family tyrosine kinase [KO:K05854] [EC:2.7.10.2]
100616957  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
100617582  [KO:K18952] [EC:2.7.11.13]
100618058  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
100618269  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.39]
103091999  CX3CL1; C-X3-C motif chemokine ligand 1 [KO:K05508]
103093665  [KO:K14624]
103094355  CXCL16; C-X-C motif chemokine ligand 16 [KO:K10035]
103095251  CXCR6; C-X-C motif chemokine receptor 6 [KO:K04191]
103096620  [KO:K05507]
103099606  [KO:K12964]
103100967  [KO:K05408]
103101025  CXCL13; C-X-C motif chemokine ligand 13 [KO:K10032]
103101147  [KO:K05408]
103101444  [KO:K12964]
103101510  [KO:K21097]
103102273  CXCL9; C-X-C motif chemokine ligand 9 [KO:K05416]
103102658  CCL25; C-C motif chemokine ligand 25 [KO:K13072]
103103530  CXCL10; C-X-C motif chemokine ligand 10 [KO:K12671]
103103873  [KO:K18952] [EC:2.7.11.13]
554186  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
554197  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
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
mdo04010  MAPK signaling pathway
mdo04060  Cytokine-cytokine receptor interaction
mdo04120  Ubiquitin mediated proteolysis
mdo04630  JAK-STAT signaling pathway
mdo04670  Leukocyte transendothelial migration
mdo04810  Regulation of actin cytoskeleton
KO pathway
ko04062   

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