Platelet-derived growth factor receptor-mediated signal transduction from endosomes
Platelet-derived growth factor receptor-mediated signal transduction from endosomes
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DOI：
10.1074/jbc.m311494200
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发表时间：
2004-02-27
影响因子：
4.8
通讯作者：
Wang, ZX
中科院分区：
文献类型：
--
作者：
Wang, Y;Pennock, SD;Wang, ZX
虽然积累的证据支持受体酪氨酸激酶的内体信号传导的概念，但大多数结果来自表皮生长因子受体（EGFR）的研究。目前尚不清楚内体信号传导的概念是否可以普遍适用于其他受体酪氨酸激酶。例如，血小板衍生生长因子受体（PDGFR）在信号传导和运输方面与EGFR非常相似；然而，对PDGFR的内体信号传导知之甚少。在这项研究中，我们采用了与我们最近关于EGFR内体信号传导的研究相同的方法来研究PDGFR的内体信号传导。我们在这次交流中表明，我们能够建立一个系统，允许内核体相关的PDGFR特异性激活，而不激活质膜相关的PDGFR，也不会破坏整个内吞作用途径。通过该系统，我们发现PDGFR的内体激活将各种信号蛋白包括Grb2、SHC、磷脂酶C-gamma1和磷脂酰肌醇3-激酶的p85 α亚基募集到内体中，并与PDGFR形成信号复合物。我们还发现，内体PDGFR信号足以激活与细胞增殖和存活有关的主要信号通路。此外，我们证明了内体PDGFR信号足以产生包括细胞增殖和细胞存活在内的生理输出。
Although accumulated evidence supports the concept of endosomal signaling of receptor tyrosine kinases, most results are generated from studies of epidermal growth factor receptor (EGFR). It is not clear whether the concept of endosomal signaling could be generally applied to the other receptor tyrosine kinases. For example, platelet-derived growth factor receptor (PDGFR) is very similar to EGFR in terms of both signaling and trafficking; however, little is known about the endosomal signaling of PDGFR. In this research, we applied the same approaches from our recent studies regarding EGFR endosomal signaling to investigate the endosomal signaling of PDGFR. We showed in this communication that we are able to establish a system that allows the specific activation of endosome-associated PDGFR without the activation of the plasma membrane-associated PDGFR and without disrupting the overall endocytosis pathway. By using this system, we showed that endosomal activation of PDGFR recruits various signaling proteins including Grb2, SHC, phospholipase C-gamma1, and the p85alpha subunit of phosphatidylinositol 3-kinase into endosomes and forms signaling complexes with PDGFR. We also showed that endosomal PDGFR signaling is sufficient to activate the major signaling pathways implicated in cell proliferation and survival. Moreover, we demonstrate that endosomal PDGFR signaling is sufficient to generate physiological output including cell proliferation and cell survival.