Additive effects of PDGF receptor beta signaling pathways in vascular smooth muscle cell development.
Additive effects of PDGF receptor beta signaling pathways in vascular smooth muscle cell development.
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DOI：
10.1371/journal.pbio.0000052
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发表时间：
2003-11
期刊：
影响因子：
9.8
通讯作者：
Soriano P
中科院分区：
文献类型：
--
作者：
Tallquist MD;French WJ;Soriano P
已知血小板衍生生长因子β受体（PDGFRβ）激活参与信号转导的许多分子，并且多年来一直是受体酪氨酸激酶信号传导的范例。我们试图通过分析阻止特定信号转导成分结合的酪氨酸-苯丙氨酸突变的等位基因系列来确定该受体下游的单个信号传导成分在体内的作用。在这里，我们发现血管平滑肌细胞/周细胞（v/p）（一种PDGFRβ依赖性细胞类型）的发生率与受体表达量和激活的信号转导通路数量相关。受体表达水平的降低或多个下游信号传导途径的破坏导致v/p显著降低。相反，RasGAP结合的丧失导致该相同细胞群的增加，暗示该效应物在减弱PDGFRβ信号中的潜在作用。结合体内和生化数据表明，与PDGFRβ信号转导相关的途径的总和决定了发育中v/p细胞的扩增。使用体内和生物化学方法，与PDGFRβ信号转导相关的途径的总和显示出确定特定PDGFRβ依赖性细胞类型的扩增
The platelet-derived growth factor β receptor (PDGFRβ) is known to activate many molecules involved in signal transduction and has been a paradigm for receptor tyrosine kinase signaling for many years. We have sought to determine the role of individual signaling components downstream of this receptor in vivo by analyzing an allelic series of tyrosine–phenylalanine mutations that prevent binding of specific signal transduction components. Here we show that the incidence of vascular smooth muscle cells/pericytes (v/p), a PDGFRβ-dependent cell type, can be correlated to the amount of receptor expressed and the number of activated signal transduction pathways. A decrease in either receptor expression levels or disruption of multiple downstream signaling pathways lead to a significant reduction in v/p. Conversely, loss of RasGAP binding leads to an increase in this same cell population, implicating a potential role for this effector in attenuating the PDGFRβ signal. The combined in vivo and biochemical data suggest that the summation of pathways associated with the PDGFRβ signal transduction determines the expansion of developing v/p cells. Using both in vivo and biochemical approaches, the summation of pathways associated with the PDGFRβ signal transduction is shown to determine the expansion of a specific PDGFRβ-dependent cell type
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