KEGG   PATHWAY: tmu04062
Entry
tmu04062                    Pathway                                
Name
Chemokine signaling pathway - Trichechus manatus latirostris (Florida manatee)
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
tmu04062  Chemokine signaling pathway
tmu04062

Other DBs
GO: 0070098
Organism
Trichechus manatus latirostris (Florida manatee) [GN:tmu]
Gene
101357988  growth-regulated protein homolog gamma-like [KO:K05505]
101346678  growth-regulated alpha protein-like [KO:K05505]
101358249  C-X-C motif chemokine 6 isoform X2 [KO:K05506]
101358515  interleukin-8 [KO:K10030]
101353256  C-X-C motif chemokine 9 [KO:K05416]
101352998  C-X-C motif chemokine 10 [KO:K12671]
101352733  C-X-C motif chemokine 11 [KO:K12672]
101347066  stromal cell-derived factor 1 [KO:K10031]
101358081  C-X-C motif chemokine 13 [KO:K10032]
101359713  C-X-C motif chemokine 16 [KO:K10035]
101346937  platelet factor 4 [KO:K05407]
101345654  C-X-C motif chemokine 14 [KO:K10033]
101357913  lymphotactin [KO:K05507]
101352858  fractalkine isoform X2 [KO:K05508]
101359659  C-C motif chemokine 1 [KO:K05514]
101358871  C-C motif chemokine 2 [KO:K14624]
101361964  regakine-1-like [KO:K05408]
101340657  C-C motif chemokine 3-like [KO:K05408]
101340395  C-C motif chemokine 3-like [KO:K05408]
101353264  C-C motif chemokine 4 [KO:K12964]
101352479  C-C motif chemokine 5 [KO:K12499]
101359398  C-C motif chemokine 8-like [KO:K16596]
101347534  eotaxin isoform X2 [KO:K16597]
101352743  C-C motif chemokine 14 [KO:K21092]
101361709  C-C motif chemokine 15 [KO:K05511]
101353007  C-C motif chemokine 16 [KO:K21093]
101360556  C-C motif chemokine 17 [KO:K21083]
101360215  C-C motif chemokine 19 [KO:K05512]
101352919  C-C motif chemokine 20 isoform X3 [KO:K14625]
101359954  C-C motif chemokine 21 [KO:K16062]
101360819  C-C motif chemokine 22 [KO:K21095]
111819701  uncharacterized protein LOC111819701 [KO:K16598]
105755989  LOW QUALITY PROTEIN: C-C motif chemokine 27 [KO:K16598]
101355148  C-C motif chemokine 28 [KO:K05513]
101342494  C-X-C chemokine receptor type 2 [KO:K05050]
101342750  C-X-C chemokine receptor type 1 [KO:K04175]
101354345  C-X-C chemokine receptor type 3 isoform X2 [KO:K04188]
101349103  C-X-C chemokine receptor type 4 isoform X1 [KO:K04189]
101348201  C-X-C chemokine receptor type 5 [KO:K04190]
101340598  C-X-C chemokine receptor type 6 [KO:K04191]
101340865  chemokine XC receptor 1 [KO:K04193]
101343179  CX3C chemokine receptor 1 [KO:K04192]
101342927  C-C chemokine receptor type 8 isoform X1 [KO:K04183]
101361721  C-C chemokine receptor type 6 [KO:K04181]
101340339  C-C chemokine receptor type 9 isoform X1 [KO:K04184]
101351151  C-C chemokine receptor type 4 [KO:K04179]
101342758  C-C chemokine receptor type 7 isoform X1 [KO:K04182]
101341117  C-C chemokine receptor type 2 [KO:K04177]
101341365  C-C chemokine receptor type 5 [KO:K04180]
101358538  C-C chemokine receptor type 1 isoform X2 [KO:K04176]
101358798  C-C chemokine receptor type 3 [KO:K04178]
101352854  C-C chemokine receptor type 10 [KO:K04185]
101354918  tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
101345231  tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
101357916  signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101348948  signal transducer and activator of transcription 2 [KO:K11221]
101342651  signal transducer and activator of transcription 3 isoform X3 [KO:K04692]
101354148  signal transducer and activator of transcription 5B [KO:K11224]
101341952  guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
101346092  guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
101343271  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101354868  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101360334  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101349290  adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
101350438  adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
101346041  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101349243  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
101341715  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101350704  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101344705  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101342638  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101348995  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101353037  tyrosine-protein kinase Lyn isoform X1 [KO:K05854] [EC:2.7.10.2]
101344005  tyrosine-protein kinase HCK isoform X1 [KO:K08893] [EC:2.7.10.2]
101361519  tyrosine-protein kinase Fgr isoform X2 [KO:K08891] [EC:2.7.10.2]
101342555  proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
101358105  SHC-transforming protein 1 isoform X1 [KO:K06279]
101359726  SHC-transforming protein 2 [KO:K17447]
101360084  SHC-transforming protein 3 [KO:K17448]
101355900  SHC-transforming protein 4 [KO:K17449]
101359012  growth factor receptor-bound protein 2 [KO:K04364]
101359592  son of sevenless homolog 1 isoform X1 [KO:K03099]
101347392  son of sevenless homolog 2 isoform X1 [KO:K03099]
101342804  GTPase HRas isoform X2 [KO:K02833]
101347525  GTPase KRas isoform X3 [KO:K07827]
101344230  GTPase NRas isoform X1 [KO:K07828]
101357840  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101353421  serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
101343332  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101340589  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101358526  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101358678  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101346849  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101359658  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101351035  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101343804  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101347746  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101354532  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289] [EC:2.7.1.153]
101352786  phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
101343689  phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
101350086  protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
101360493  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101356099  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101350197  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101354741  forkhead box protein O3 [KO:K09408]
101341290  inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101351256  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101347574  NF-kappa-B essential modulator isoform X1 [KO:K07210]
101355353  NF-kappa-B inhibitor alpha [KO:K04734]
101357924  NF-kappa-B inhibitor beta [KO:K02581]
101351866  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101361706  transcription factor p65 [KO:K04735]
101352047  bcl2-associated agonist of cell death [KO:K02158]
101361052  glycogen synthase kinase-3 alpha [KO:K08822] [EC:2.7.11.26]
101349186  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101347980  tyrosine-protein kinase ITK/TSK isoform X2 [KO:K07363] [EC:2.7.10.2]
101343550  guanine nucleotide exchange factor VAV2 [KO:K05730]
101347509  proto-oncogene vav [KO:K05730]
101353271  guanine nucleotide exchange factor VAV3 isoform X2 [KO:K05730]
101356054  ras-related C3 botulinum toxin substrate 1 [KO:K04392]
101355428  ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
101360313  ras-related C3 botulinum toxin substrate 3 [KO:K07861]
101343358  serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
101361943  cell division control protein 42 homolog isoform X1 [KO:K04393]
101348260  wiskott-Aldrich syndrome protein isoform X2 [KO:K05747]
101356840  transforming protein RhoA [KO:K04513]
101345959  rho-associated protein kinase 2 isoform X4 [KO:K17388] [EC:2.7.11.1]
101350742  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
101345319  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
101355136  guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
101348280  guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
101341327  guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
101352593  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 isoform X1 [KO:K07826]
101342107  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
101357541  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
101345326  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
101347845  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 isoform X2 [KO:K04543]
111821467  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
111819711  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
101341777  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
101351188  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
111819060  putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
101351136  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
101342034  guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
101360148  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
101346362  phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein [KO:K12365]
101340853  engulfment and cell motility protein 1 [KO:K12366]
101357939  dedicator of cytokinesis protein 2 isoform X1 [KO:K12367]
101351714  focal adhesion kinase 1 isoform X2 [KO:K05725] [EC:2.7.10.2]
101359554  paxillin isoform X1 [KO:K05760]
101346861  breast cancer anti-estrogen resistance protein 1 [KO:K05726]
101355809  crk-like protein [KO:K04438]
101342748  adapter molecule crk isoform X1 [KO:K04438]
101354947  protein-tyrosine kinase 2-beta isoform X3 [KO:K05871] [EC:2.7.10.2]
101347192  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
101352296  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101349967  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
101344242  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
101361375  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
101359597  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
101346393  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
101347941  RAS guanyl-releasing protein 2 [KO:K12361]
101352801  ras-related protein Rap-1A [KO:K04353]
101348129  ras-related protein Rap-1b [KO:K07836]
101355481  partitioning defective 3 homolog isoform X1 [KO:K04237]
101352570  T-lymphoma invasion and metastasis-inducing protein 1 isoform X1 [KO:K05731]
101356454  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101355651  protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
101343104  neutrophil cytosol factor 1 isoform X1 [KO:K08011]
101351547  rhodopsin kinase [KO:K00909] [EC:2.7.11.14]
101343459  rhodopsin kinase [KO:K00909] [EC:2.7.11.14]
101346329  beta-adrenergic receptor kinase 1 isoform X2 [KO:K00910] [EC:2.7.11.15]
101357163  beta-adrenergic receptor kinase 2 isoform X1 [KO:K00910] [EC:2.7.11.15]
101341711  G protein-coupled receptor kinase 6 isoform X5 [KO:K08291] [EC:2.7.11.16]
101350552  G protein-coupled receptor kinase 5 isoform X1 [KO:K08291] [EC:2.7.11.16]
101361031  G protein-coupled receptor kinase 4 [KO:K08291] [EC:2.7.11.16]
101354945  beta-arrestin-1 [KO:K04439]
101341907  beta-arrestin-2 isoform X2 [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
tmu04010  MAPK signaling pathway
tmu04060  Cytokine-cytokine receptor interaction
tmu04120  Ubiquitin mediated proteolysis
tmu04630  JAK-STAT signaling pathway
tmu04670  Leukocyte transendothelial migration
tmu04810  Regulation of actin cytoskeleton
KO pathway
ko04062   
LinkDB

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