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PMID: 10037796 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Similarities and differences in RANTES- and (AOP)-RANTES-triggered signals: implications for chemotaxis.

The Journal of cell biology ·Vol. 144 ·No. 4 ·1999-02-22 ·Pages 755-65

Rodríguez-Frade JM, Vila-Coro AJ, Martín A, Nieto M, Sánchez-Madrid F, Proudfoot AE, Wells TN, Martínez-A C, Mellado M

Abstract

Chemokines are a family of proinflammatory cytokines that attract and activate specific types of leukocytes. Chemokines mediate their effects via interaction with seven transmembrane G protein-coupled receptors (GPCR). Using CCR5-transfected HEK-293 cells, we show that both the CCR5 ligand, RANTES, as well as its derivative, aminooxypentane (AOP)- RANTES, trigger immediate responses such as Ca2+ influx, receptor dimerization, tyrosine phosphorylation, and Galphai as well as JAK/STAT association to the receptor. In contrast to RANTES, (AOP)-RANTES is unable to trigger late responses, as measured by the association of focal adhesion kinase (FAK) to the chemokine receptor complex, impaired cell polarization required for migration, or chemotaxis. The results are discussed in the context of the dissociation of the late signals, provoked by the chemokines required for cell migration, from early signals.

MeSH Terms
Cell Adhesion Molecules/metabolism Cell Line Chemokine CCL5/analogs & derivatives,physiology Chemotaxis/physiology DNA-Binding Proteins/metabolism Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases GTP-Binding Proteins/metabolism Humans Janus Kinase 1 Milk Proteins Phosphorylation Protein-Tyrosine Kinases/metabolism Receptors, CCR5/genetics,physiology STAT5 Transcription Factor Signal Transduction/physiology Trans-Activators/metabolism Transfection Tyrosine/metabolism
Chemicals
Cell Adhesion Molecules Chemokine CCL5 DNA-Binding Proteins Milk Proteins Receptors, CCR5 STAT5 Transcription Factor Trans-Activators aminooxypentane-RANTES Tyrosine Protein-Tyrosine Kinases Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases JAK1 protein, human Janus Kinase 1 PTK2 protein, human GTP-Binding Proteins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Rodríguez-Frade J M
Department of Immunology and Oncology, Centro Nacional de Biotecnolog¿ia, CSIC/UAM, Campus de Cantoblanco, E-28049 Madrid, Spain.
Vila-Coro A J
Martín A
Nieto M
Sánchez-Madrid F
Proudfoot A E
Wells T N
Martínez-A C
Mellado M
References (56)
56 references, click to expand
  1. Expression of chemokine receptors by subsets of neurons in the central nervous system.
    J Immunol. 1997 Mar 15;158(6):2882-90 PMID: 9058825
  2. RANTES induces tyrosine kinase activity of stably complexed p125FAK and ZAP-70 in human T cells.
    J Exp Med. 1996 Sep 1;184(3):873-82 PMID: 9064347
  3. Potent inhibition of HIV-1 infectivity in macrophages and lymphocytes by a novel CCR5 antagonist.
    Science. 1997 Apr 11;276(5310):276-9 PMID: 9092481
  4. The differential ability of IL-8 and neutrophil-activating peptide-2 to induce attenuation of chemotaxis is mediated by their divergent capabilities to phosphorylate CXCR2 (IL-8 receptor B).
    J Immunol. 1997 Jun 15;158(12):5927-33 PMID: 9190946
  5. HIV coreceptor downregulation as antiviral principle: SDF-1alpha-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication.
    J Exp Med. 1997 Jul 7;186(1):139-46 PMID: 9207008
  6. Polarization of chemokine receptors to the leading edge during lymphocyte chemotaxis.
    J Exp Med. 1997 Jul 7;186(1):153-8 PMID: 9207004
  7. Chemokines.
    Blood. 1997 Aug 1;90(3):909-28 PMID: 9242519
  8. The amino-terminal domain of the CCR2 chemokine receptor acts as coreceptor for HIV-1 infection.
    J Clin Invest. 1997 Aug 1;100(3):497-502 PMID: 9239395
  9. Jaks, STATs, cytokine signal transduction, and immunoregulation: are we there yet?
    Immunity. 1997 Jul;7(1):1-11 PMID: 9252115
  10. Molecular mechanism of desensitization of the chemokine receptor CCR-5: receptor signaling and internalization are dissociable from its role as an HIV-1 co-receptor.
    EMBO J. 1997 Aug 1;16(15):4606-16 PMID: 9303305
  11. Dissociation of chemotaxis from agonist-induced receptor internalization in a lymphocyte cell line transfected with CCR2B. Evidence that directed migration does not require rapid modulation of signaling at the receptor level.
    J Biol Chem. 1997 Oct 3;272(40):25037-42 PMID: 9312111
  12. Blocking chemokine receptors.
    J Exp Med. 1997 Oct 20;186(8):1189-91 PMID: 9379143
  13. Mechanism of transdominant inhibition of CCR5-mediated HIV-1 infection by ccr5delta32.
    J Biol Chem. 1997 Dec 5;272(49):30603-6 PMID: 9388191
  14. Receptors induce chemotaxis by releasing the betagamma subunit of Gi, not by activating Gq or Gs.
    Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14489-94 PMID: 9405640
  15. Chemotaxis in a lymphocyte cell line transfected with C-C chemokine receptor 2B: evidence that directed migration is mediated by betagamma dimers released by activation of Galphai-coupled receptors.
    Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14495-9 PMID: 9405641
  16. RANTES and MIP-1alpha activate stats in T cells.
    J Biol Chem. 1998 Jan 2;273(1):309-14 PMID: 9417081
  17. Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2.
    Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2985-90 PMID: 9501202
  18. Characterization of the CCR2 chemokine receptor: functional CCR2 receptor expression in B cells.
    J Immunol. 1997 Dec 1;159(11):5576-84 PMID: 9548499
  19. Aminooxypentane-RANTES induces CCR5 internalization but inhibits recycling: a novel inhibitory mechanism of HIV infectivity.
    J Exp Med. 1998 Apr 20;187(8):1215-24 PMID: 9547333
  20. Chemokines and leukocyte traffic.
    Nature. 1998 Apr 9;392(6676):565-8 PMID: 9560152
  21. Small molecule inhibitor of HIV-1 cell fusion blocks chemokine receptor-mediated function.
    J Leukoc Biol. 1998 Jul;64(1):6-13 PMID: 9665268
  22. The chemokine monocyte chemotactic protein 1 triggers Janus kinase 2 activation and tyrosine phosphorylation of the CCR2B receptor.
    J Immunol. 1998 Jul 15;161(2):805-13 PMID: 9670957
  23. Chemokines and T lymphocytes: more than an attraction.
    Immunity. 1998 Jul;9(1):1-11 PMID: 9697831
  24. The alpha-chemokine, stromal cell-derived factor-1alpha, binds to the transmembrane G-protein-coupled CXCR-4 receptor and activates multiple signal transduction pathways.
    J Biol Chem. 1998 Sep 4;273(36):23169-75 PMID: 9722546
  25. Pyk2 and Src-family protein-tyrosine kinases compensate for the loss of FAK in fibronectin-stimulated signaling events but Pyk2 does not fully function to enhance FAK- cell migration.
    EMBO J. 1998 Oct 15;17(20):5933-47 PMID: 9774338
  26. The chemokine monocyte chemoattractant protein-1 induces functional responses through dimerization of its receptor CCR2.
    Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3628-33 PMID: 10097088
  27. Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES.
    Nature. 1990 Oct 18;347(6294):669-71 PMID: 1699135
  28. Specific interactions of chemoattractant factor receptors with G-proteins.
    J Biol Chem. 1993 May 15;268(14):10139-44 PMID: 8486684
  29. Life at the leading edge: the formation of cell protrusions.
    Annu Rev Cell Biol. 1993;9:411-44 PMID: 8280467
  30. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines.
    Adv Immunol. 1994;55:97-179 PMID: 8304236
  31. The molecular biology of leukocyte chemoattractant receptors.
    Annu Rev Immunol. 1994;12:593-633 PMID: 8011292
  32. FMLP activates Ras and Raf in human neutrophils. Potential role in activation of MAP kinase.
    J Clin Invest. 1994 Aug;94(2):815-23 PMID: 8040337
  33. Lymphotactin: a cytokine that represents a new class of chemokine.
    Science. 1994 Nov 25;266(5189):1395-9 PMID: 7973732
  34. Actions of the chemotactic cytokines MCP-1, MCP-2, MCP-3, RANTES, MIP-1 alpha and MIP-1 beta on human monocytes.
    Eur J Immunol. 1995 Jan;25(1):64-8 PMID: 7531149
  35. IL-8-induced signal transduction in T lymphocytes involves receptor-mediated activation of phospholipases C and D.
    J Immunol. 1995 Apr 15;154(8):3654-66 PMID: 7706709
  36. Chemokines, leukocyte trafficking, and inflammation.
    Curr Opin Immunol. 1994 Dec;6(6):865-73 PMID: 7710711
  37. Integrins and signal transduction pathways: the road taken.
    Science. 1995 Apr 14;268(5208):233-9 PMID: 7716514
  38. A comparison of post-receptor signal transduction events in Jurkat cells transfected with either IL-8R1 or IL-8R2. Chemokine mediated activation of p42/p44 MAP-kinase (ERK-2).
    FEBS Lett. 1995 May 8;364(2):211-4 PMID: 7750573
  39. Chemokine expression in murine experimental allergic encephalomyelitis.
    J Neuroimmunol. 1995 May;58(2):167-76 PMID: 7539012
  40. A conserved NPLFY sequence contributes to agonist binding and signal transduction but is not an internalization signal for the type 1 angiotensin II receptor.
    J Biol Chem. 1995 Jul 14;270(28):16602-9 PMID: 7622467
  41. Chemoattractant signaling and leukocyte activation.
    Blood. 1995 Sep 1;86(5):1649-60 PMID: 7654998
  42. Ca(2+)- and calcineurin-dependent recycling of an integrin to the front of migrating neutrophils.
    Nature. 1995 Sep 7;377(6544):75-9 PMID: 7544874
  43. Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis.
    J Immunol. 1995 Oct 15;155(8):3877-88 PMID: 7561094
  44. Cyclic AMP-increasing agents interfere with chemoattractant-induced respiratory burst in neutrophils as a result of the inhibition of phosphatidylinositol 3-kinase rather than receptor-operated Ca2+ influx.
    J Biol Chem. 1995 Oct 6;270(40):23816-22 PMID: 7559558
  45. Activation of dual T cell signaling pathways by the chemokine RANTES.
    Science. 1995 Sep 22;269(5231):1727-30 PMID: 7569902
  46. Integrin function: molecular hierarchies of cytoskeletal and signaling molecules.
    J Cell Biol. 1995 Nov;131(3):791-805 PMID: 7593197
  47. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells.
    Science. 1995 Dec 15;270(5243):1811-5 PMID: 8525373
  48. STATs: signal transducers and activators of transcription.
    Cell. 1996 Feb 9;84(3):331-4 PMID: 8608586
  49. RANTES and MCP-3 antagonists bind multiple chemokine receptors.
    J Biol Chem. 1996 May 3;271(18):10521-7 PMID: 8631850
  50. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1.
    Science. 1996 Jun 28;272(5270):1955-8 PMID: 8658171
  51. A peptide derived from a beta2-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation.
    J Biol Chem. 1996 Jul 5;271(27):16384-92 PMID: 8663163
  52. HIV blocked by chemokine antagonist.
    Nature. 1996 Oct 3;383(6599):400 PMID: 8837769
  53. Distinct expression and function of the novel mouse chemokine monocyte chemotactic protein-5 in lung allergic inflammation.
    J Exp Med. 1996 Nov 1;184(5):1939-51 PMID: 8920881
  54. Eosinophil recruitment to the lung in a murine model of allergic inflammation. The role of T cells, chemokines, and adhesion receptors.
    J Clin Invest. 1996 Nov 15;98(10):2332-45 PMID: 8941651
  55. A new class of membrane-bound chemokine with a CX3C motif.
    Nature. 1997 Feb 13;385(6617):640-4 PMID: 9024663
  56. Conformational changes required in the human growth hormone receptor for growth hormone signaling.
    J Biol Chem. 1997 Apr 4;272(14):9189-96 PMID: 9083050
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.144.4.755
Published
1999-02-22
Pages
755-65
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2132943
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.144.4.755 PMC Full Text View journal details
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