KEGG PATHWAY: map04062

PATHWAY: map04062

Entry

map04062                    Pathway

Name

Chemokine signaling pathway

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

map04062

Chemokine signaling pathway

Other DBs

GO:

0070098

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

map04010

MAPK signaling pathway

map04060

Cytokine-cytokine receptor interaction

map04120

Ubiquitin mediated proteolysis

map04630

JAK-STAT signaling pathway

map04670

Leukocyte transendothelial migration

map04810

Regulation of actin cytoskeleton

KO pathway

ko04062

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