KEGG   PATHWAY: map04062Help
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
BRITE hierarchy
Pathway map
map04062  Chemokine signaling pathway
map04062

Ortholog table
Disease
H00540  Osteoporosis, lymphedema, anhydrotic ectodermal dysplasia with immunodeficiency (OLEDAID)
H00645  Incontinentia pigmenti
H00882  Cocoon syndrome
H00931  Growth hormone insensitivity with immunodeficiency
H01109  Chronic mucocutaneous candidiasis
Other DBs
GO: 0070098
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
KO pathway
ko04062   

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