Abstract
Cell differentiation is often associated with a block in the cell cycle. Growth factor signaling has been reported to be impaired in differentiated cells, due to the withdrawal of growth factors or to transcriptional down-regulation of their receptors. Our proposal is that the down regulation of growth factor signaling may be achieved through an alternative pathway: the decrease of growth factor receptor activation and the ensuing inhibition of intracellular pathways leading the cell to division. Here we report that platelet-derived growth factor receptor (PDGFr) signaling is down-regulated during muscle differentiation, although its expression level remains unchanged. PDGFr signaling inhibition is achieved through a decrease in the receptor tyrosine phosphorylation level, in particular of Tyr716, Tyr751, Tyr857 and Tyr1021, leading to down-regulation of intracellular signaling pathways. Furthermore, during myogenesis, the espression level of several phosphotyrosine phosphatases (PTPs) increases and most of them shift toward the reduced/activated state. We propose a causal link between the down-regulation of PDGFr tyrosine phosphorylation and the increases in PTP specific activity during myogenesis.
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Received 23 July 2003; received after revision 15 September 2003; accepted 9 October 2003
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Fiaschi, T., Chiarugi, P., Buricchi, F. et al. Down-regulation of platelet-derived growth factor receptor signaling during myogenesis. CMLS, Cell. Mol. Life Sci. 60, 2721–2735 (2003). https://doi.org/10.1007/s00018-003-3293-3
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DOI: https://doi.org/10.1007/s00018-003-3293-3