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| Subject Categories: Signal Transduction | Neuroscience |
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| The EMBO Journal
(2002) 21, 1957–1966, doi: 10.1093/emboj/21.8.1957 |
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The oligodendrocyte precursor mitogen PDGF stimulates proliferation by activation of  v 3 integrins |
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| Wia Baron1, 2, Sanford J. Shattil3 and Charles ffrench-Constant1, 4 |
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1 Department of Medical Genetics, University of Cambridge, and Cambridge Centre for Brain Repair, ED Adrian Building, University Forvie Site, Cambridge CB2 2PY, UK 2 Present address: Department of Membrane Cell Biology, University of Groningen, Faculty of Medical Sciences, A.Deusinglaan 1, NL-9713 AV, Groningen, The Netherlands 3 Departments of Vascular Biology and Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA 4 Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK To whom correspondence should be addressed Charles ffrench-Constant, cfc@mole.bio.cam.ac.uk Received 19 December 2001; Revised 25 February 2002; Accepted 26 February 2002. |
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| Abstract |
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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) substrates that bind v3 integrin. Upon PDGF-AA exposure and v3 engagement, a physical co-association between both receptors was demonstrated, confirming the interaction between these signalling pathways. Furthermore, we found that PDGFR stimulated a protein kinase C-dependent activation of integrin v3, 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. |
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| Keywords: activation, extracellular matrix, integrin, PDGF, WOW-1 |
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