KEGG   PATHWAY: rno04062
rno04062                    Pathway                                

Chemokine signaling pathway - Rattus norvegicus (rat)
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.
Organismal Systems; Immune system
Pathway map
rno04062  Chemokine signaling pathway

Other DBs
GO: 0070098
Rattus norvegicus (rat) [GN:rno]
81503  Cxcl1; growth-regulated alpha protein precursor [KO:K05505]
114105  Cxcl2; C-X-C motif chemokine 2 precursor [KO:K05505]
171551  Cxcl3; C-X-C motif chemokine 3 precursor [KO:K05505]
60665  Cxcl6; C-X-C motif chemokine 5 precursor [KO:K05506]
246358  Ppbp; platelet basic protein precursor [KO:K10029]
246759  Cxcl9; C-X-C motif chemokine 9 precursor [KO:K05416]
245920  Cxcl10; C-X-C motif chemokine 10 precursor [KO:K12671]
305236  Cxcl11; C-X-C motif chemokine 11 precursor [KO:K12672]
24772  Cxcl12; stromal cell-derived factor 1 isoform beta precursor [KO:K10031]
498335  Cxcl13; C-X-C motif chemokine 13 precursor [KO:K10032]
497942  Cxcl16; C-X-C motif chemokine 16 precursor [KO:K10035]
360918  Pf4; platelet factor 4 precursor [KO:K05407]
306748  Cxcl14; C-X-C motif chemokine 14 precursor [KO:K10033]
171371  Xcl1; lymphotactin precursor [KO:K05507]
89808  Cx3cl1; fractalkine precursor [KO:K05508]
688605  Ccl1; C-C motif chemokine 1 precursor [KO:K05514]
287562  Ccl12; chemokine (C-C motif) ligand 12 precursor [KO:K14624]
24770  Ccl2; C-C motif chemokine 2 precursor [KO:K14624]
25542  Ccl3; C-C motif chemokine 3 precursor [KO:K05408]
116637  Ccl4; C-C motif chemokine 4 precursor [KO:K12964]
81780  Ccl5; C-C motif chemokine 5 precursor [KO:K12499]
287910  Ccl6; C-C motif chemokine 6 precursor [KO:K05510]
287561  Ccl7; C-C motif chemokine 7 precursor [KO:K05509]
360579  Ccl9; C-C motif chemokine 9 precursor [KO:K22671]
29397  Ccl11; eotaxin precursor [KO:K16597]
117518  Ccl17; C-C motif chemokine 17 precursor [KO:K21083]
362506  Ccl19; C-C motif chemokine 19 precursor [KO:K05512]
29538  Ccl20; C-C motif chemokine 20 precursor [KO:K14625]
298006  Ccl21; C-C motif chemokine 21 precursor [KO:K16062]
117551  Ccl22; C-C motif chemokine 22 precursor [KO:K21095]
288593  Ccl24; C-C motif chemokine 24 precursor [KO:K21097]
360750  Ccl25; C-C motif chemokine 25 precursor [KO:K13072]
685958  Ccl26; C-C motif chemokine 26 precursor [KO:K21096]
362505  Ccl27; C-C motif chemokine 27 [KO:K16598]
114492  Ccl28; C-C motif chemokine 28 precursor [KO:K05513]
29385  Cxcr2; C-X-C chemokine receptor type 2 [KO:K05050]
54258  Cxcr1; C-X-C chemokine receptor type 1 [KO:K04175]
84475  Cxcr3; C-X-C chemokine receptor type 3 [KO:K04188]
60628  Cxcr4; C-X-C chemokine receptor type 4 [KO:K04189]
29363  Cxcr5; C-X-C chemokine receptor type 5 [KO:K04190]
100124593  Cxcr6; C-X-C chemokine receptor type 6 [KO:K04191]
301086  Xcr1; chemokine XC receptor 1 [KO:K04193]
171056  Cx3cr1; CX3C chemokine receptor 1 [KO:K04192]
301066  Ccr8; C-C chemokine receptor type 8 [KO:K04183]
308163  Ccr6; C-C chemokine receptor type 6 [KO:K04181]
282832  Ccr9; C-C chemokine receptor type 9 [KO:K04184]
171054  Ccr4; C-C chemokine receptor type 4 [KO:K04179]
287673  Ccr7; C-C chemokine receptor type 7 precursor [KO:K04182]
60463  Ccr2; C-C chemokine receptor type 2 [KO:K04177]
117029  Ccr5; C-C chemokine receptor type 5 [KO:K04180]
57301  Ccr1; C-C chemokine receptor type 1 [KO:K04176]
301088  Ccr1l1; C-C chemokine receptor 1-like protein 1 [KO:K04176]
117027  Ccr3; C-C chemokine receptor type 3 [KO:K04178]
363682  Ccr10; C-C chemokine receptor type 10 [KO:K04185]
24514  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:]
25326  Jak3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:]
25124  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform beta [KO:K11220]
288774  Stat2; signal transducer and activator of transcription 2 [KO:K11221]
25125  Stat3; signal transducer and activator of transcription 3 [KO:K04692]
25126  Stat5b; signal transducer and activator of transcription 5B [KO:K11224]
25686  Gnai1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
25643  Gnai3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
81664  Gnai2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
305509  Adcy1; adenylate cyclase type 1 [KO:K08041] [EC:]
81636  Adcy2; adenylate cyclase type 2 [KO:K08042] [EC:]
64508  Adcy3; adenylate cyclase type 3 [KO:K08043] [EC:]
54223  Adcy4; adenylate cyclase type 4 [KO:K08044] [EC:]
64532  Adcy5; adenylate cyclase type 5 [KO:K08045] [EC:]
25289  Adcy6; adenylate cyclase type 6 isoform 2 [KO:K08046] [EC:]
84420  Adcy7; adenylate cyclase type 7 [KO:K08047] [EC:]
29241  Adcy8; adenylate cyclase type 8 [KO:K08048] [EC:]
302950  Adcy9; adenylate cyclase type 9 [KO:K08049] [EC:]
25636  Prkaca; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:]
293508  Prkacb; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:]
81515  Lyn; tyrosine-protein kinase Lyn isoform A [KO:K05854] [EC:]
25734  Hck; tyrosine-protein kinase HCK [KO:K08893] [EC:]
79113  Fgr; tyrosine-protein kinase Fgr [KO:K08891] [EC:]
83805  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:]
85385  Shc1; SHC-transforming protein 1 isoform b [KO:K06279]
314612  Shc2; SHC-transforming protein 2 [KO:K17447]
114858  Shc3; SHC-transforming protein 3 [KO:K17448]
679845  Shc4; SHC-transforming protein 4 [KO:K17449]
81504  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
85384  Sos2; son of sevenless homolog 2 [KO:K03099]
313845  Sos1; son of sevenless homolog 1 [KO:K03099]
293621  Hras; GTPase HRas [KO:K02833]
367858  GTPase HRas [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:]
114486  Braf; serine/threonine-protein kinase B-raf isoform X6 [KO:K04365] [EC:]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
298947  Pik3cg; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289] [EC:]
497931  Pik3r5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290]
497932  Pik3r6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290]
25522  Prkcz; protein kinase C zeta type [KO:K18952] [EC:]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:]
294515  Foxo3; forkhead box protein O3 [KO:K09408]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
81525  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
309165  Rela; transcription factor p65 [KO:K04735]
64639  Bad; bcl2-associated agonist of cell death [KO:K02158]
50686  Gsk3a; glycogen synthase kinase-3 alpha [KO:K08822] [EC:]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:]
363577  Itk; tyrosine-protein kinase ITK/TSK [KO:K07363] [EC:]
25156  Vav1; proto-oncogene vav [KO:K05730]
295378  Vav3; guanine nucleotide exchange factor VAV3 [KO:K05730]
296603  Vav2; guanine nucleotide exchange factor VAV2 [KO:K05730]
363875  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
366957  Rac2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
29431  Pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:]
64465  Cdc42; cell division control protein 42 homolog [KO:K04393]
317371  Was; wiskott-Aldrich syndrome protein [KO:K05747]
117273  Rhoa; transforming protein RhoA [KO:K04513]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
81762  Rock1; rho-associated protein kinase 1 [KO:K04514] [EC:]
25537  Rock2; rho-associated protein kinase 2 [KO:K17388] [EC:]
24400  Gnb1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
81667  Gnb2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
60449  Gnb3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
294962  Gnb4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
83579  Gnb5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539]
80850  Gng2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
114117  Gng3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
114118  Gng4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
79218  Gng5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
108349548  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
58979  Gng7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
245986  Gng8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
114119  Gng10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
64199  Gng11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
114120  Gng12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
685513  Gng14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347]
685451  Gng13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
680149  Gngt1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
690825  Gngt2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
311647  Prex1; phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein [KO:K12365]
361251  Elmo1; engulfment and cell motility protein 1 [KO:K12366]
360509  Dock2; dedicator of cytokinesis protein 2 isoform X1 [KO:K12367]
25614  Ptk2; focal adhesion kinase 1 [KO:K05725] [EC:]
360820  Pxn; paxillin [KO:K05760]
25414  Bcar1; breast cancer anti-estrogen resistance protein 1 [KO:K05726]
54245  Crk; adapter molecule crk [KO:K04438]
287942  Crkl; crk-like protein [KO:K04438]
50646  Ptk2b; protein-tyrosine kinase 2-beta [KO:K05871] [EC:]
81666  Gnaq; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
24654  Plcb1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:]
29322  Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:]
85240  Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:]
25031  Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:]
25738  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:]
29337  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:]
361714  Rasgrp2; RAS guanyl-releasing protein 2 [KO:K12361]
295347  Rap1a; ras-related protein Rap-1A [KO:K04353]
171337  Rap1b; ras-related protein Rap-1b [KO:K07836]
81918  Pard3; partitioning defective 3 homolog [KO:K04237]
304109  Tiam1; T-lymphoma invasion and metastasis-inducing protein 1 [KO:K05731]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:]
170538  Prkcd; protein kinase C delta type [KO:K06068] [EC:]
114553  Ncf1; neutrophil cytosolic factor 1 [KO:K08011]
81760  Grk1; rhodopsin kinase GRK1 [KO:K00909] [EC:]
25238  Grk2; beta-adrenergic receptor kinase 1 [KO:K00910] [EC:]
25372  Grk3; beta-adrenergic receptor kinase 2 [KO:K00910] [EC:]
59075  Grk5; G protein-coupled receptor kinase 5 [KO:K08291] [EC:]
59076  Grk6; G protein-coupled receptor kinase 6 isoform c [KO:K08291] [EC:]
59077  Grk4; G protein-coupled receptor kinase 4 [KO:K08291] [EC:]
25387  Arrb1; beta-arrestin-1 [KO:K04439]
25388  Arrb2; beta-arrestin-2 [KO:K04439]
C00076  Calcium cation
C00165  Diacylglycerol
C00575  3',5'-Cyclic AMP
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Wong MM, Fish EN
Chemokines: attractive mediators of the immune response.
Semin Immunol 15:5-14 (2003)
Curnock AP, Logan MK, Ward SG
Chemokine signalling: pivoting around multiple phosphoinositide 3-kinases.
Immunology 105:125-36 (2002)
Olson TS, Ley K
Chemokines and chemokine receptors in leukocyte trafficking.
Am J Physiol Regul Integr Comp Physiol 283:R7-28 (2002)
Busillo JM, Benovic JL
Regulation of CXCR4 signaling.
Biochim Biophys Acta 1768:952-63 (2007)
Mellado M, Rodriguez-Frade JM, Manes S, Martinez-A C
Chemokine signaling and functional responses: the role of receptor dimerization and TK pathway activation.
Annu Rev Immunol 19:397-421 (2001)
Knall C, Young S, Nick JA, Buhl AM, Worthen GS, Johnson GL
Interleukin-8 regulation of the Ras/Raf/mitogen-activated protein kinase pathway in human neutrophils.
J Biol Chem 271:2832-8 (1996)
Patrussi L, Ulivieri C, Lucherini OM, Paccani SR, Gamberucci A, Lanfrancone L, Pelicci PG, Baldari CT
p52Shc is required for CXCR4-dependent signaling and chemotaxis in T cells.
Blood 110:1730-8 (2007)
Sai J, Raman D, Liu Y, Wikswo J, Richmond A
Parallel phosphatidylinositol 3-kinase (PI3K)-dependent and Src-dependent pathways lead to CXCL8-mediated Rac2 activation and chemotaxis.
J Biol Chem 283:26538-47 (2008)
Hauck CR, Klingbeil CK, Schlaepfer DD
Focal adhesion kinase functions as a receptor-proximal signaling component required for directed cell migration.
Immunol Res 21:293-303 (2000)
Chandrasekar B, Bysani S, Mummidi S
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.
J Biol Chem 279:3188-96 (2004)
Smith L, Webb A, Ward SG
T-lymphocyte navigation and migration: beyond the PI3K paradigm.
Biochem Soc Trans 35:193-8 (2007)
Huttenrauch F, Pollok-Kopp B, Oppermann M
G protein-coupled receptor kinases promote phosphorylation and beta-arrestin-mediated internalization of CCR5 homo- and hetero-oligomers.
J Biol Chem 280:37503-15 (2005)
Thelen M, Stein JV
How chemokines invite leukocytes to dance.
Nat Immunol 9:953-9 (2008)
Ward SG, Marelli-Berg FM
Mechanisms of chemokine and antigen-dependent T-lymphocyte navigation.
Biochem J 418:13-27 (2009)
Schwartzberg PL, Finkelstein LD, Readinger JA
TEC-family kinases: regulators of T-helper-cell differentiation.
Nat Rev Immunol 5:284-95 (2005)
Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL.
Tec family kinases in T lymphocyte development and function.
Annu Rev Immunol 23:549-600 (2005)
Ticchioni M, Essafi M, Jeandel PY, Davi F, Cassuto JP, Deckert M, Bernard A
Homeostatic chemokines increase survival of B-chronic lymphocytic leukemia cells through inactivation of transcription factor FOXO3a.
Oncogene 26:7081-91 (2007)
Korchak HM, Rossi MW, Kilpatrick LE
Selective role for beta-protein kinase C in signaling for O-2 generation but not degranulation or adherence in differentiated HL60 cells.
J Biol Chem 273:27292-9 (1998)
Johnson Z, Power CA, Weiss C, Rintelen F, Ji H, Ruckle T, Camps M, Wells TN, Schwarz MK, Proudfoot AE, Rommel C
Chemokine inhibition--why, when, where, which and how?
Biochem Soc Trans 32:366-77 (2004)
Zhelev DV, Alteraifi A
Signaling in the motility responses of the human neutrophil.
Ann Biomed Eng 30:356-70 (2002)
Bach TL, Chen QM, Kerr WT, Wang Y, Lian L, Choi JK, Wu D, Kazanietz MG, Koretzky GA, Zigmond S, Abrams CS
Phospholipase cbeta is critical for T cell chemotaxis.
J Immunol 179:2223-7 (2007)
Hornstein I, Alcover A, Katzav S
Vav proteins, masters of the world of cytoskeleton organization.
Cell Signal 16:1-11 (2004)
rno04010  MAPK signaling pathway
rno04060  Cytokine-cytokine receptor interaction
rno04120  Ubiquitin mediated proteolysis
rno04630  JAK-STAT signaling pathway
rno04670  Leukocyte transendothelial migration
rno04810  Regulation of actin cytoskeleton
KO pathway

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