The oligodendrocyte precursor mitogen PDGF stimulates proliferation by activation of αvβ3 integrins

Baron, Wia, Shattil, Sanford J. and Ffrench-Constant, Charles ORCID: (2002) The oligodendrocyte precursor mitogen PDGF stimulates proliferation by activation of αvβ3 integrins. EMBO Journal, 21 (8). pp. 1957-1966. ISSN 0261-4189

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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) substrate that bind αvβ3 integrin. Upon PDGF-AA exposure and αvβ3 engagement, a physical co-association between both receptors was demonstrated, confirming the interaction between these signalling pathways. Furthermore, we found that PDGFaR stimulated a protein kinase C-dependent activation of integrin αvβ3, 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.

Item Type: Article
Uncontrolled Keywords: activation,extracellular matrix,integrin,pdgf,wow-1,neuroscience(all),molecular biology,biochemistry, genetics and molecular biology(all),immunology and microbiology(all) ,/dk/atira/pure/subjectarea/asjc/2800
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 16 Jul 2022 13:30
Last Modified: 23 Oct 2022 03:57
DOI: 10.1093/emboj/21.8.1957

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