The emerging complexity of PDGFRs: activation, internalization and signal attenuation.
The emerging complexity of PDGFRs: activation, internalization and signal attenuation.
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DOI：
10.1042/bst20200004
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发表时间：
2020-06-30
影响因子：
3.9
通讯作者：
Fantauzzo KA
中科院分区：
文献类型：
--
作者：
Rogers MA;Fantauzzo KA
受体酪氨酸激酶的血小板衍生生长因子受体（PDGFR）家族允许细胞与环境通信以调节多种细胞活动。在这里，我们强调最近的数据调查激活后的单个PDGFRs的结构组成，揭示了整个受体在细胞外配体结合和二聚化的传播的重要性。此外，我们回顾了正在进行的研究表明受体内化和信号衰减的PDGFR活性的调节的意义。与内化机制的相互作用、来自内体的信号传导、受体降解和受体再循环是细胞微调PDGFR对生长因子刺激的反应的生理手段。在这篇综述中，我们讨论了生物物理，结构，在硅片和生化数据，这些机制提供了证据。我们进一步强调了PDGFRα和PDGFRβ信号传导之间的共性和差异，揭示了知识的关键差距。总之，这篇评论提供了一个结论性的总结PDGFR领域的状态，并强调需要新的技术，以充分阐明PDGFR激活，内化和信号衰减的机制。
The platelet-derived growth factor receptor (PDGFR) family of receptor tyrosine kinases allows cells to communicate with the environment to regulate diverse cellular activities. Here, we highlight recent data investigating the structural makeup of individual PDGFRs upon activation, revealing the importance of the whole receptor in the propagation of extracellular ligand binding and dimerization. Furthermore, we review ongoing research demonstrating the significance of receptor internalization and signal attenuation in the regulation of PDGFR activity. Interactions with internalization machinery, signaling from endosomes, receptor degradation and receptor recycling are physiological means by which cells fine-tune PDGFR responses to growth factor stimulation. In this review, we discuss the biophysical, structural, in silico and biochemical data that have provided evidence for these mechanisms. We further highlight the commonalities and differences between PDGFRα and PDGFRβ signaling, revealing critical gaps in knowledge. In total, this review provides a conclusive summary on the state of the PDGFR field and underscores the need for novel techniques to fully elucidate the mechanisms of PDGFR activation, internalization and signal attenuation.