Entry |
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Name |
Chemokine signaling pathway - Rattus norvegicus (rat)
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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.
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Class |
Organismal Systems; Immune system
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Pathway map |

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Other DBs |
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Organism |
Rattus norvegicus (rat) [GN: rno]
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Gene |
81503 | Cxcl1; growth-regulated alpha protein precursor [KO:K05505] |
60665 | Cxcl6; C-X-C motif chemokine 5 precursor [KO:K05506] |
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] |
306748 | Cxcl14; C-X-C motif chemokine 14 precursor [KO:K10033] |
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] |
81780 | Ccl5; C-C motif chemokine 5 precursor [KO:K12499] |
29538 | Ccl20; C-C motif chemokine 20 precursor [KO:K14625] |
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] |
287673 | Ccr7; C-C chemokine receptor type 7 precursor [KO:K04182] |
301088 | Ccr1l1; C-C chemokine receptor 1-like protein 1 [KO:K04176] |
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] |
85385 | Shc1; SHC-transforming protein 1 isoform b [KO:K06279] |
81504 | Grb2; growth factor receptor-bound protein 2 [KO:K04364] |
85243 | Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153] |
170911 | Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153] |
366508 | Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153] |
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:2.7.1.153] |
497931 | Pik3r5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290] |
497932 | Pik3r6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290] |
81736 | Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580] |
64639 | Bad; bcl2-associated agonist of cell death [KO:K02158] |
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] |
64465 | Cdc42; cell division control protein 42 homolog [KO:K04393] |
297173 | RSA-14-44; ras homolog gene family, member A [KO:K04513] |
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] |
25414 | Bcar1; breast cancer anti-estrogen resistance protein 1 [KO:K05726] |
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:3.1.4.11] |
29322 | Plcb3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11] |
85240 | Plcb2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11] |
25031 | Plcb4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11] |
25738 | Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11] |
29337 | Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11] |
81918 | Pard3; partitioning defective 3 homolog [KO:K04237] |
304109 | Tiam1; T-lymphoma invasion and metastasis-inducing protein 1 [KO:K05731] |
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Compound |
C01245 | D-myo-Inositol 1,4,5-trisphosphate |
C05981 | Phosphatidylinositol-3,4,5-trisphosphate |
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Reference |
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Authors |
Wong MM, Fish EN |
Title |
Chemokines: attractive mediators of the immune response. |
Journal |
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Reference |
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Authors |
Curnock AP, Logan MK, Ward SG |
Title |
Chemokine signalling: pivoting around multiple phosphoinositide 3-kinases. |
Journal |
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Reference |
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Authors |
Olson TS, Ley K |
Title |
Chemokines and chemokine receptors in leukocyte trafficking. |
Journal |
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Reference |
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Authors |
Busillo JM, Benovic JL |
Title |
Regulation of CXCR4 signaling. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Hauck CR, Klingbeil CK, Schlaepfer DD |
Title |
Focal adhesion kinase functions as a receptor-proximal signaling component required for directed cell migration. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Smith L, Webb A, Ward SG |
Title |
T-lymphocyte navigation and migration: beyond the PI3K paradigm. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Thelen M, Stein JV |
Title |
How chemokines invite leukocytes to dance. |
Journal |
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Reference |
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Authors |
Ward SG, Marelli-Berg FM |
Title |
Mechanisms of chemokine and antigen-dependent T-lymphocyte navigation. |
Journal |
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Reference |
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Authors |
Schwartzberg PL, Finkelstein LD, Readinger JA |
Title |
TEC-family kinases: regulators of T-helper-cell differentiation. |
Journal |
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Reference |
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Authors |
Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL. |
Title |
Tec family kinases in T lymphocyte development and function. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Zhelev DV, Alteraifi A |
Title |
Signaling in the motility responses of the human neutrophil. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Hornstein I, Alcover A, Katzav S |
Title |
Vav proteins, masters of the world of cytoskeleton organization. |
Journal |
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Related pathway |
rno04060 | Cytokine-cytokine receptor interaction |
rno04670 | Leukocyte transendothelial migration |
rno04810 | Regulation of actin cytoskeleton |
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KO pathway |
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