Entry
Name
Chemokine signaling pathway - Rattus norvegicus (rat)
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
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Rattus norvegicus (rat) [GN:
rno ]
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 isoform 2 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; C-C motif chemokine 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-3 [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 ]
367858 Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833 ]
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 ]
134484121 LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform-like [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 isoform 2 [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 ]
688319 Rac3; ras-related C3 botulinum toxin substrate 3 [KO:K07861 ]
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 ]
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 ]
25414 Bcar1; breast cancer anti-estrogen resistance protein 1 isoform 3 [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 ]
171337 Rap1b; ras-related protein Rap-1b precursor [KO:K07836 ]
81918 Pard3; partitioning defective 3 homolog [KO:K04237 ]
304109 Tiam1; rho guanine nucleotide exchange factor TIAM1 [KO:K05731 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Wong MM, Fish EN
Title
Chemokines: attractive mediators of the immune response.
Journal
Reference
Authors
Curnock AP, Logan MK, Ward SG
Title
Chemokine signalling: pivoting around multiple phosphoinositide 3-kinases.
Journal
Reference
Authors
Olson TS, Ley K
Title
Chemokines and chemokine receptors in leukocyte trafficking.
Journal
Reference
Authors
Busillo JM, Benovic JL
Title
Regulation of CXCR4 signaling.
Journal
Reference
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
Reference
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
Reference
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
Reference
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
Reference
Authors
Hauck CR, Klingbeil CK, Schlaepfer DD
Title
Focal adhesion kinase functions as a receptor-proximal signaling component required for directed cell migration.
Journal
Reference
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
Reference
Authors
Smith L, Webb A, Ward SG
Title
T-lymphocyte navigation and migration: beyond the PI3K paradigm.
Journal
Reference
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
Reference
Authors
Thelen M, Stein JV
Title
How chemokines invite leukocytes to dance.
Journal
Reference
Authors
Ward SG, Marelli-Berg FM
Title
Mechanisms of chemokine and antigen-dependent T-lymphocyte navigation.
Journal
Reference
Authors
Schwartzberg PL, Finkelstein LD, Readinger JA
Title
TEC-family kinases: regulators of T-helper-cell differentiation.
Journal
Reference
Authors
Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL.
Title
Tec family kinases in T lymphocyte development and function.
Journal
Reference
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
Reference
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
Reference
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
Reference
Authors
Zhelev DV, Alteraifi A
Title
Signaling in the motility responses of the human neutrophil.
Journal
Reference
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
Reference
Authors
Hornstein I, Alcover A, Katzav S
Title
Vav proteins, masters of the world of cytoskeleton organization.
Journal
Related pathway
rno04060 Cytokine-cytokine receptor interaction
rno04670 Leukocyte transendothelial migration
rno04810 Regulation of actin cytoskeleton
KO pathway
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