Catarzi Serena, Biagioni Chiara, Giannoni Elisa, Favilli Fabio, Marcucci Tommaso, Iantomasi Teresa, Vincenzini Maria Teresa
Department of Biochemical Sciences, University of Florence, viale Morgagni 50, 50134, Florence, Italy.
Biochim Biophys Acta. 2005 Sep 10;1745(2):166-75. doi: 10.1016/j.bbamcr.2005.03.004. Epub 2005 Mar 22.
This study identifies some early events contributing to the redox regulation of platelet-derived growth factor receptor (PDGFr) activation and its signalling in NIH3T3 fibroblasts. We demonstrate for the first time that the redox regulation of PDGFr tyrosine autophosphorylation and its signalling are related to NADPH oxidase activity through protein kinase C (PKC) and phosphoinositide-3-kinase (PI3K) activation and H2O2 production. This event is also essential for complete PDGF-induced activation of c-Src kinase by Tyr416 phosphorylation, and the involvement of c-Src kinase on H2O2-induced PDGFr tyrosine phosphorylation is demonstrated, suggesting a role of this kinase on the redox regulation of PDGFr activation. Finally, it has been determined that not only PI3K activity, but also PKC activity, are related to NADPH oxidase activation due to PDGF stimulation in NIH3T3 cells, as it occurs in non-phagocyte cells. Therefore, we suggest a redox circuit whereby, upon PDGF stimulation, PKC, PI3K and NADPH oxidase activity contribute to complete c-Src kinase activation, thus promoting maximal phosphorylation and activation of PDGFr tyrosine phosphorylation.
本研究确定了一些促成血小板衍生生长因子受体（PDGFr）激活及其在NIH3T3成纤维细胞中信号传导的氧化还原调节的早期事件。我们首次证明，PDGFr酪氨酸自磷酸化及其信号传导的氧化还原调节通过蛋白激酶C（PKC）和磷酸肌醇-3-激酶（PI3K）的激活以及H2O2的产生与NADPH氧化酶活性相关。这一事件对于通过Tyr416磷酸化完全激活PDGF诱导的c-Src激酶也是必不可少的，并且证明了c-Src激酶参与H2O2诱导的PDGFr酪氨酸磷酸化，表明该激酶在PDGFr激活的氧化还原调节中发挥作用。最后，已经确定，不仅PI3K活性，而且PKC活性，都与NIH3T3细胞中PDGF刺激引起的NADPH氧化酶激活有关，就像在非吞噬细胞中发生的那样。因此，我们提出了一个氧化还原回路，即PDGF刺激后，PKC、PI3K和NADPH氧化酶活性有助于完全激活c-Src激酶，从而促进PDGFr酪氨酸磷酸化的最大程度磷酸化和激活。
