Down-regulation of platelet-derived growth factor receptor signaling during myogenesis.

Cell Mol Life Sci. 2003 Dec;60(12):2721-35. Down-regulation of platelet-derived growth factor receptor signaling during myogenesis. Fiaschi T, Chiarugi P, Buricchi F, Giannoni E, Taddei ML, Magnelli L, Cozzi G, Raugei G, Ramponi G. Source Dipartimento di Scienze Biochimiche, Università di Firenze, viale Morgagni 50, 50134 Firenze, Italy. 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 expression 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. PMID: 14685695 [PubMed - indexed for MEDLINE]