Down-regulation of platelet-derived growth factor receptor signaling during myogenesis.
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.
Fiaschi
T
T
Dipartimento di Scienze Biochimiche, Università di Firenze, viale Morgagni 50, 50134 Firenze, Italy.
Chiarugi
P
P
Buricchi
F
F
Giannoni
E
E
Taddei
M L
ML
Magnelli
L
L
Cozzi
G
G
Raugei
G
G
Ramponi
G
G
D000818:Animals; D015536:Down-Regulation; D051379:Mice; D024510:Muscle Development / Q000502:physiology*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D017382:Reactive Oxygen Species; D017479:Receptors, Platelet-Derived Growth Factor; D017027:Protein Tyrosine Phosphatases