The oligodendrocyte precursor mitogen PDGF stimulates proliferation by activation of alpha(v)beta3 integrins.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Author(s): Baron W;Baron W; Shattil SJ; ffrench-Constant C
  • Source:
    The EMBO journal [EMBO J] 2002 Apr 15; Vol. 21 (8), pp. 1957-66.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Wiley Blackwell Country of Publication: England NLM ID: 8208664 Publication Model: Print Cited Medium: Print ISSN: 0261-4189 (Print) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE
    • Publication Information:
      Publication: 2014- : London : Wiley Blackwell
      Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-
    • Subject Terms:
      Signal Transduction*; Mitogens/*pharmacology ; Oligodendroglia/*drug effects ; Platelet-Derived Growth Factor/*pharmacology ; Receptors, Vitronectin/*metabolism ; Stem Cells/*drug effects; Animals ; Cell Division ; Cells, Cultured ; Dose-Response Relationship, Drug ; Enzyme Activation ; Oligodendroglia/cytology ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Kinase C/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Platelet-Derived Growth Factor alpha/metabolism ; Stem Cells/cytology ; Vitronectin/metabolism
    • Abstract:
      Central nervous system development requires precise and localized regulation of neural precursor behaviour. Here we show how the interaction between growth factor and integrin signalling pathways provides a mechanism for such precision in oligodendrocyte progenitor (OP) proliferation. While physiological concentrations of platelet-derived growth factor (PDGF) were not in themselves sufficient to promote OP proliferation, they did so on extracellular matrix (ECM) substrates that bind alpha(v)beta3 integrin. Upon PDGF-AA exposure and alpha(v)beta3 engagement, a physical co-association between both receptors was demonstrated, confirming the interaction between these signalling pathways. Furthermore, we found that PDGFalphaR stimulated a protein kinase C-dependent activation of integrin alpha(v)beta3, which in turn induced OP proliferation via a phosphatidylinositol 3-kinase-dependent signalling pathway. These studies establish a mechanism by which OP proliferation is dependent on the availability of both an ECM ligand and a mitogenic growth factor. Growth factor- mediated integrin activation is the critical integrative step in proliferation signalling, and ensures that the response of neural precursor cells to long-range cues can be regulated by their cellular neighbours, allowing precise control of cell behaviour during development.
    • References:
      J Biol Chem. 1999 Jul 30;274(31):21609-16. (PMID: 10419468)
      Gene. 1999 Aug 5;236(1):79-86. (PMID: 10433968)
      J Neurosci Res. 2000 Feb 15;59(4):477-88. (PMID: 10679786)
      J Neurobiol. 1999 Nov 15;41(3):385-98. (PMID: 10526317)
      Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13813-8. (PMID: 10570155)
      Mol Cell Neurosci. 2000 Mar;15(3):314-29. (PMID: 10736207)
      Mol Biol Cell. 2000 Apr;11(4):1457-69. (PMID: 10749942)
      Development. 2000 May;127(9):1961-9. (PMID: 10751184)
      J Biol Chem. 2000 Jun 30;275(26):20217-22. (PMID: 10779523)
      Science. 2000 Sep 8;289(5485):1754-7. (PMID: 10976069)
      EMBO J. 2000 Oct 16;19(20):5396-405. (PMID: 11032807)
      J Biol Chem. 2000 Dec 22;275(51):39867-73. (PMID: 10964931)
      Mol Cell. 2000 Oct;6(4):851-60. (PMID: 11090623)
      J Biol Chem. 2001 Mar 2;276(9):6689-94. (PMID: 11053419)
      Matrix Biol. 2001 Feb;20(1):13-22. (PMID: 11246000)
      Curr Biol. 2001 Feb 20;11(4):232-41. (PMID: 11250151)
      J Biol Chem. 2001 Apr 13;276(15):11830-7. (PMID: 11150298)
      Curr Biol. 2001 Jul 10;11(13):1028-38. (PMID: 11470407)
      Curr Biol. 2001 Jul 10;11(13):1039-43. (PMID: 11470408)
      Development. 2001 Jul;128(13):2485-96. (PMID: 11493565)
      J Cell Sci. 2001 Jul;114(Pt 14):2553-60. (PMID: 11683383)
      J Cell Biol. 1980 Jun;85(3):890-902. (PMID: 6248568)
      Nature. 1985 Jan 17-23;313(5999):223-5. (PMID: 3969137)
      Dev Neurosci. 1985;7(3):133-60. (PMID: 2866949)
      Cell. 1988 Apr 22;53(2):309-19. (PMID: 2834067)
      J Neurosci Res. 1988 Oct-Dec;21(2-4):199-209. (PMID: 3216421)
      EMBO J. 1989 Apr;8(4):1049-56. (PMID: 2545439)
      Proc Natl Acad Sci U S A. 1990 Aug;87(16):6368-72. (PMID: 2201028)
      J Neurosci Res. 1990 Nov;27(3):400-7. (PMID: 2097382)
      J Biol Chem. 1991 Aug 25;266(24):15771-81. (PMID: 1874734)
      Development. 1991 May;112(1):161-76. (PMID: 1685113)
      Science. 1992 Mar 27;255(5052):1707-10. (PMID: 1553558)
      Cell. 1992 Apr 3;69(1):11-25. (PMID: 1555235)
      J Bone Miner Res. 1992 Mar;7(3):345-51. (PMID: 1585837)
      Science. 1992 Aug 14;257(5072):973-7. (PMID: 1380182)
      Development. 1993 Apr;117(4):1183-98. (PMID: 8404525)
      Biochem J. 1993 Dec 1;296 ( Pt 2):297-301. (PMID: 8257416)
      J Biol Chem. 1994 Jan 14;269(2):960-7. (PMID: 7507113)
      Neuron. 1994 May;12(5):935-42. (PMID: 8185952)
      J Neurosci. 1994 Aug;14(8):4716-30. (PMID: 8046446)
      J Cell Biol. 1994 Sep;126(5):1287-98. (PMID: 8063864)
      Curr Opin Genet Dev. 1994 Aug;4(4):569-74. (PMID: 7524834)
      Cancer Res. 1994 Dec 1;54(23):6106-14. (PMID: 7954456)
      Development. 1994 Dec;120(12):3497-506. (PMID: 7821217)
      Curr Opin Cell Biol. 1994 Oct;6(5):747-51. (PMID: 7833054)
      Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7686-9. (PMID: 7644477)
      J Cell Biol. 1995 Nov;131(3):791-805. (PMID: 7593197)
      J Cell Biol. 1996 Feb;132(3):475-85. (PMID: 8636223)
      J Neurosci Res. 1996 Feb 1;43(3):299-314. (PMID: 8714519)
      Neuron. 1996 Aug;17(2):229-43. (PMID: 8780647)
      J Neurosci. 1996 Nov 15;16(22):7240-52. (PMID: 8929432)
      Mol Biol Cell. 1996 Dec;7(12):1939-51. (PMID: 8970156)
      Annu Rev Cell Dev Biol. 1996;12:697-715. (PMID: 8970741)
      EMBO J. 1997 Sep 15;16(18):5600-7. (PMID: 9312019)
      J Neurosci. 1997 Dec 1;17(23):9122-32. (PMID: 9364059)
      Adv Exp Med Biol. 1997;429:69-77. (PMID: 9413566)
      Glia. 1997 Dec;21(4):350-60. (PMID: 9419010)
      J Cell Sci. 1998 Feb;111 ( Pt 4):469-78. (PMID: 9443896)
      Mol Biol Cell. 1998 Feb;9(2):277-90. (PMID: 9450954)
      Trends Biochem Sci. 1998 Jan;23(1):30-4. (PMID: 9478133)
      J Neuropathol Exp Neurol. 1998 Mar;57(3):205-17. (PMID: 9600212)
      Neuron. 1998 Jul;21(1):63-75. (PMID: 9697852)
      J Cell Biol. 1998 Dec 28;143(7):2081-92. (PMID: 9864377)
      Development. 1999 Feb;126(3):457-67. (PMID: 9876175)
      Dev Biol. 1999 Apr 1;208(1):166-88. (PMID: 10075850)
      EMBO J. 1999 Apr 15;18(8):2165-73. (PMID: 10205170)
    • Grant Information:
      R01 HL056595 United States HL NHLBI NIH HHS; HL56595 United States HL NHLBI NIH HHS
    • Accession Number:
      0 (Mitogens)
      0 (Platelet-Derived Growth Factor)
      0 (Receptors, Vitronectin)
      0 (Vitronectin)
      0 (platelet-derived growth factor A)
      EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
      EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
      EC 2.7.11.13 (Protein Kinase C)
    • Publication Date:
      Date Created: 20020416 Date Completed: 20020606 Latest Revision: 20181113
    • Publication Date:
      20231215
    • Accession Number:
      PMC125971
    • Accession Number:
      10.1093/emboj/21.8.1957
    • Accession Number:
      11953315