Artificial Control of Subtype-Specific Platelet-Derived Growth Factor-Receptor Signaling
Artificial Control of Subtype-Specific Platelet-Derived Growth Factor-Receptor Signaling
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DOI：
10.1254/jphs.09136sc
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发表时间：
2009-11-01
影响因子：
3.5
通讯作者：
Hirose, Kenzo
中科院分区：
文献类型：
--
作者：
Isa, Masayuki;Ohta, Yusaku;Hirose, Kenzo
血小板衍生生长因子（PDGF）信号传导通过两种受体亚型控制各种生理功能：PDGF受体（PDGFR）α和PDGFR β。然而，由于缺乏区分亚型特异性信号的药理学工具，我们对其作用的理解是有限的。我们通过将配体结合域截短的PDGFR β与抗荧光素单链抗体相结合来开发嵌合受体，期望寡聚荧光素作为人工激动剂来控制PDGFR β特异性信号传导。结果表明，钙动员，Cdc42激活，和细胞迁移引起的人工配体特异性表达嵌合受体的细胞。我们的方法有望有助于了解PDGFRs在各种细胞功能中的亚型特异性作用。
Platelet-derived growth factor (PDGF) signaling controls various physiological functions via two receptor subtypes: PDGF receptor (PDGFR) alpha and PDGFR beta. Nevertheless, our understanding of their roles is limited because of a lack of pharmacological tools to discriminate subtype-specific signaling. We developed a chimeric receptor by combining ligand-binding-domain truncated PDGFR beta with anti-fluorescein single chain antibody, expecting the control of PDGFR beta-specific signaling by oligomerized fluorescein as an artificial agonist. Results show that calcium mobilization, Cdc42 activation, and cell migration were elicited specifically by the artificial ligand in cells expressing the chimeric receptor. Our method is expected to be useful to understand the subtype-specific roles of PDGFRs in various cellular functions.