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Pathway Description
CXCR4 Signaling Pathway
Bos taurus
Category:
Protein Pathway
Sub-Categories:
Cytokine Signaling
Immunological
Pathogen-Activated Signaling
Kinase Signaling
Gene Regulatory
Cellular Response
Created: 2018-09-20
Last Updated: 2019-08-16
CXCR4 is a chemokine G-protein-coupled receptor. Chemokine receptors couple to the pertussis toxin-sensitive Gi proteins. It is involved in organogenesis, hematopoiesis, and the immune response. Chemokine stromal cell-derived factor 1 (SDF-1) binds CXCR4. CXCR4 is also a co-receptor for HIV and is involved in the metastasis of some cancers. Pertussis toxin ADP-ribosylates guanine nucleotide binding protein alpha inhibiting (Gai) proteins inhibiting GPCR/Gi coupling. Activated Gai inhibits adenylyl cyclase and activates tyrosine kinases, while activated guanine nucleotide binding protein beta and gamma activate PI3K - regulating gene transcription, cell migration, and cell adhesion. PLC is activated to cause the cleavage of PIP2 to IP3 and DG. This leads to the increase of calcium from the endoplasmic reticulum and the activation of protein kinase C.
References
CXCR4 Signaling Pathway References
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Michel T, Winslow JW, Smith JA, Seidman JG, Neer EJ: Molecular cloning and characterization of cDNA encoding the GTP-binding protein alpha i and identification of a related protein, alpha h. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7663-7. doi: 10.1073/pnas.83.20.7663.
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Pubmed: 2414128
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Hurley JB, Fong HK, Teplow DB, Dreyer WJ, Simon MI: Isolation and characterization of a cDNA clone for the gamma subunit of bovine retinal transducin. Proc Natl Acad Sci U S A. 1984 Nov;81(22):6948-52. doi: 10.1073/pnas.81.22.6948.
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Yatsunami K, Pandya BV, Oprian DD, Khorana HG: cDNA-derived amino acid sequence of the gamma subunit of GTPase from bovine rod outer segments. Proc Natl Acad Sci U S A. 1985 Apr;82(7):1936-40. doi: 10.1073/pnas.82.7.1936.
Pubmed: 2984674
Tao L, Pandey S, Simon MI, Fong HK: Structure of the bovine transducin gamma subunit gene and analysis of promoter function in transgenic mice. Exp Eye Res. 1993 Apr;56(4):497-507. doi: 10.1006/exer.1993.1063.
Pubmed: 8500562
Matsui Y, Kikuchi A, Kawata M, Kondo J, Teranishi Y, Takai Y: Molecular cloning of smg p21B and identification of smg p21 purified from bovine brain and human platelets as smg p21B. Biochem Biophys Res Commun. 1990 Jan 30;166(2):1010-6. doi: 10.1016/0006-291x(90)90911-6.
Pubmed: 2105724
Harhay GP, Sonstegard TS, Keele JW, Heaton MP, Clawson ML, Snelling WM, Wiedmann RT, Van Tassell CP, Smith TP: Characterization of 954 bovine full-CDS cDNA sequences. BMC Genomics. 2005 Nov 23;6:166. doi: 10.1186/1471-2164-6-166.
Pubmed: 16305752
Sneyers M, Kettmann R, Massart S, Renaville R, Burny A, Portetelle D: Cloning and characterization of a cDNA encoding the beta-subunit of the bovine insulin-like growth factor-1 receptor. DNA Seq. 1991;1(6):405-6.
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Panetti TS, Hannah DF, Avraamides C, Gaughan JP, Marcinkiewicz C, Huttenlocher A, Mosher DF: Extracellular matrix molecules regulate endothelial cell migration stimulated by lysophosphatidic acid. J Thromb Haemost. 2004 Sep;2(9):1645-56. doi: 10.1111/j.1538-7836.2004.00902.x.
Pubmed: 15333043
Avraamides C, Bromberg ME, Gaughan JP, Thomas SM, Tsygankov AY, Panetti TS: Hic-5 promotes endothelial cell migration to lysophosphatidic acid. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H193-203. doi: 10.1152/ajpheart.00728.2006. Epub 2007 Mar 2.
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Yamaji D, Kitamura H, Kimura K, Matsushita Y, Okada H, Shiina T, Morimatsu M, Saito M: Cloning of bovine MAIL and its mRNA expression in white blood cells of Holstein cows. Vet Immunol Immunopathol. 2004 Apr;98(3-4):175-84. doi: 10.1016/j.vetimm.2003.12.004.
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Stahl ML, Ferenz CR, Kelleher KL, Kriz RW, Knopf JL: Sequence similarity of phospholipase C with the non-catalytic region of src. Nature. 1988 Mar 17;332(6161):269-72. doi: 10.1038/332269a0.
Pubmed: 2831461
Kim JW, Sim SS, Kim UH, Nishibe S, Wahl MI, Carpenter G, Rhee SG: Tyrosine residues in bovine phospholipase C-gamma phosphorylated by the epidermal growth factor receptor in vitro. J Biol Chem. 1990 Mar 5;265(7):3940-3.
Pubmed: 1689310
Wahl MI, Nishibe S, Kim JW, Kim H, Rhee SG, Carpenter G: Identification of two epidermal growth factor-sensitive tyrosine phosphorylation sites of phospholipase C-gamma in intact HSC-1 cells. J Biol Chem. 1990 Mar 5;265(7):3944-8.
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Nakamura F, Ogata K, Shiozaki K, Kameyama K, Ohara K, Haga T, Nukada T: Identification of two novel GTP-binding protein alpha-subunits that lack apparent ADP-ribosylation sites for pertussis toxin. J Biol Chem. 1991 Jul 5;266(19):12676-81.
Pubmed: 1905731
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0064625
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