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PMID: 18404419 Published · ppublish English Journal Article

Activation of transcription factors by extracellular nucleotides in immune and related cell types.

Purinergic signalling ·Vol. 3 ·No. 1-2 ·2007-03-00 ·Pages 59-69

Armstrong S, Korcok J, Sims SM, Dixon SJ

Abstract

Extracellular nucleotides, acting through P2 receptors, can regulate gene expression via intracellular signaling pathways that control the activity of transcription factors. Relatively little is known about the activation of transcription factors by nucleotides in immune cells. The NF-kappaB family of transcription factors is critical for many immune and inflammatory responses. Nucleotides released from damaged or stressed cells can act alone through certain P2 receptors to alter NF-kappaB activity or they can enhance responses induced by pathogen-associated molecules such as LPS. Nucleotides have also been shown to regulate the activity of other transcription factors (AP-1, NFAT, CREB and STAT) in immune and related cell types. Here, we provide an overview of transcription factors shown to be activated by nucleotides in immune cells, and describe what is known about their mechanisms of activation and potential functions. Furthermore, we propose areas for future work in this new and expanding field.

Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Armstrong Souzan
CIHR Group in Skeletal Development and Remodeling, Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada, N6A 5C1.
Korcok Jasminka
Sims Stephen M
Dixon S Jeffrey
References (52)
52 references, click to expand
  1. P2X7/P2Z purinoreceptor-mediated activation of transcription factor NFAT in microglial cells.
    J Biol Chem. 1999 May 7;274(19):13205-10 PMID: 10224077
  2. Extracellular ATP activates transcription factor NF-kappaB through the P2Z purinoreceptor by selectively targeting NF-kappaB p65.
    J Cell Biol. 1997 Dec 29;139(7):1635-43 PMID: 9412459
  3. Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5'-polyphosphates.
    Bioorg Med Chem Lett. 2001 Jan 22;11(2):157-60 PMID: 11206448
  4. Tumor necrosis factor alpha-induced apoptosis in astrocytes is prevented by the activation of P2Y6, but not P2Y4 nucleotide receptors.
    Biochem Pharmacol. 2003 Mar 15;65(6):923-31 PMID: 12623123
  5. Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts.
    Biochem Biophys Res Commun. 2003 May 30;305(2):211-4 PMID: 12745060
  6. The isoquinoline derivative KN-62 a potent antagonist of the P2Z-receptor of human lymphocytes.
    Br J Pharmacol. 1997 Apr;120(8):1483-90 PMID: 9113369
  7. Regulation of the expression of the inflammatory nitric oxide synthase (NOS2) by cyclic AMP.
    FASEB J. 1999 Dec;13(15):2125-37 PMID: 10593859
  8. Purinergic mechanism in the immune system: A signal of danger for dendritic cells.
    Purinergic Signal. 2005 Sep;1(3):205-9 PMID: 18404505
  9. Transcriptional regulation of T lymphocyte development and function.
    Annu Rev Immunol. 1999;17:149-87 PMID: 10358756
  10. Role of nuclear factor-kappaB in the immune system and bone.
    Immunol Rev. 2005 Dec;208:80-7 PMID: 16313342
  11. Novel data point to a broader mechanism of action of oxidized ATP: the P2X7 receptor is not the only target.
    Br J Pharmacol. 2003 Oct;140(3):441-3 PMID: 14522840
  12. Transcriptional networks in developing and mature B cells.
    Nat Rev Immunol. 2005 Jun;5(6):497-508 PMID: 15928681
  13. Extracellular ATP and neurodegeneration.
    Curr Drug Targets CNS Neurol Disord. 2003 Dec;2(6):403-12 PMID: 14683468
  14. AP-1 in mouse development and tumorigenesis.
    Oncogene. 2001 Apr 30;20(19):2401-12 PMID: 11402336
  15. IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy.
    J Clin Invest. 2005 Oct;115(10):2625-32 PMID: 16200195
  16. Pyrimidinoceptor potentiation of macrophage PGE(2) release involved in the induction of nitric oxide synthase.
    Br J Pharmacol. 2000 Jun;130(4):777-86 PMID: 10864883
  17. Phylogenetic perspectives in innate immunity.
    Science. 1999 May 21;284(5418):1313-8 PMID: 10334979
  18. Phosphorylated CREB binds specifically to the nuclear protein CBP.
    Nature. 1993 Oct 28;365(6449):855-9 PMID: 8413673
  19. Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor.
    Cell. 1992 Aug 21;70(4):585-93 PMID: 1505025
  20. Purinergic receptor modulation of BV-2 microglial cell activity: potential involvement of p38 MAP kinase and CREB.
    J Neuroimmunol. 2005 Sep;166(1-2):113-25 PMID: 15979729
  21. Receptors for purines and pyrimidines.
    Pharmacol Rev. 1998 Sep;50(3):413-92 PMID: 9755289
  22. Role of histone acetylation in the control of gene expression.
    Biochem Cell Biol. 2005 Jun;83(3):344-53 PMID: 15959560
  23. KN-62, 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazi ne, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II.
    J Biol Chem. 1990 Mar 15;265(8):4315-20 PMID: 2155222
  24. PKC- and ERK-dependent activation of I kappa B kinase by lipopolysaccharide in macrophages: enhancement by P2Y receptor-mediated CaMK activation.
    Br J Pharmacol. 2001 Nov;134(5):1055-65 PMID: 11682454
  25. Protein-DNA array-based identification of transcription factor activities regulated by interaction with the glucocorticoid receptor.
    J Biol Chem. 2004 Sep 10;279(37):38480-5 PMID: 15247296
  26. AP-1 subunits: quarrel and harmony among siblings.
    J Cell Sci. 2004 Dec 1;117(Pt 25):5965-73 PMID: 15564374
  27. Purinergic receptors modulate MAP kinases and transcription factors that control microglial inflammatory gene expression.
    Neurochem Int. 2006 Jul;49(2):204-14 PMID: 16735081
  28. Evidence for nucleotide receptor modulation of cross talk between MAP kinase and NF-kappa B signaling pathways in murine RAW 264.7 macrophages.
    Am J Physiol Cell Physiol. 2004 Apr;286(4):C923-30 PMID: 14684387
  29. Extracellular ATP: a growth factor for vascular smooth muscle cells.
    Gen Pharmacol. 1998 Jul;31(1):1-8 PMID: 9595270
  30. Apoptosis in bone physiology and disease.
    Mol Pathol. 1997 Jun;50(3):132-7 PMID: 9292147
  31. Molecular physiology of P2X receptors.
    Physiol Rev. 2002 Oct;82(4):1013-67 PMID: 12270951
  32. Shared pathways of IkappaB kinase-induced SCF(betaTrCP)-mediated ubiquitination and degradation for the NF-kappaB precursor p105 and IkappaBalpha.
    Mol Cell Biol. 2001 Feb;21(4):1024-35 PMID: 11158290
  33. The JAK/STAT signaling pathway.
    J Cell Sci. 2004 Mar 15;117(Pt 8):1281-3 PMID: 15020666
  34. Pyrimidinoceptor-mediated potentiation of inducible nitric-oxide synthase induction in J774 macrophages. Role of intracellular calcium.
    J Biol Chem. 1998 Nov 6;273(45):29754-63 PMID: 9792689
  35. MEKK2 is required for T-cell receptor signals in JNK activation and interleukin-2 gene expression.
    J Biol Chem. 2001 May 4;276(18):14784-90 PMID: 11278622
  36. Signaling through P2X7 receptor in human T cells involves p56lck, MAP kinases, and transcription factors AP-1 and NF-kappa B.
    J Biol Chem. 2003 Jan 17;278(3):1549-60 PMID: 12424250
  37. Requirement for NF-kappaB in osteoclast and B-cell development.
    Genes Dev. 1997 Dec 15;11(24):3482-96 PMID: 9407039
  38. P2Y6 nucleotide receptors activate NF-kappaB and increase survival of osteoclasts.
    J Biol Chem. 2005 Apr 29;280(17):16909-15 PMID: 15722352
  39. Bone resorption by osteoclasts.
    Science. 2000 Sep 1;289(5484):1504-8 PMID: 10968780
  40. Mechanistic insight into osteoclast differentiation in osteoimmunology.
    J Mol Med (Berl). 2005 Mar;83(3):170-9 PMID: 15776286
  41. Signaling to NF-kappaB.
    Genes Dev. 2004 Sep 15;18(18):2195-224 PMID: 15371334
  42. What turns CREB on?
    Cell Signal. 2004 Nov;16(11):1211-27 PMID: 15337521
  43. Oxidized ATP (oATP) attenuates proinflammatory signaling via P2 receptor-independent mechanisms.
    Br J Pharmacol. 2003 Oct;140(3):507-19 PMID: 14522842
  44. Tilling the chromatin landscape: emerging methods for the discovery and profiling of protein-DNA interactions.
    Biochem Cell Biol. 2005 Aug;83(4):525-34 PMID: 16094456
  45. Extracellular nucleotides act through P2X7 receptors to activate NF-kappaB in osteoclasts.
    J Bone Miner Res. 2004 Apr;19(4):642-51 PMID: 15005852
  46. Signaling by STATs.
    Arthritis Res Ther. 2004;6(4):159-68 PMID: 15225360
  47. TLR signaling.
    Cell Death Differ. 2006 May;13(5):816-25 PMID: 16410796
  48. NF-kappaB regulation in the immune system.
    Nat Rev Immunol. 2002 Oct;2(10):725-34 PMID: 12360211
  49. Multiple nuclear factors interact with the immunoglobulin enhancer sequences.
    Cell. 1986 Aug 29;46(5):705-16 PMID: 3091258
  50. Protein kinase C theta cooperates with Vav1 to induce JNK activity in T-cells.
    J Biol Chem. 2001 Jun 8;276(23):20022-8 PMID: 11274147
  51. NFAT proteins: key regulators of T-cell development and function.
    Nat Rev Immunol. 2005 Jun;5(6):472-84 PMID: 15928679
  52. Extracellular ATP induces cytokine expression and apoptosis through P2X7 receptor in murine mast cells.
    J Immunol. 2005 Apr 1;174(7):3880-90 PMID: 15778342
Article Info
Journal
Purinergic signalling
Abbr.
Purinergic Signal
ISSN
1573-9538
DOI
10.1007/s11302-006-9037-8
Published
2007-03-00
Epub
2007-00-03
Pages
59-69
Language
English
Region
Netherlands
NLM ID
101250499
PMCID
PMC2096760
External Links
PubMed source DOI: 10.1007/s11302-006-9037-8 PMC Full Text View journal details
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