Identifying Transmembrane Interactions in Receptor Protein Tyrosine Phosphatase Homodimerization and Heterodimerization.
Identifying Transmembrane Interactions in Receptor Protein Tyrosine Phosphatase Homodimerization and Heterodimerization.
复制标题
识别受体蛋白酪氨酸磷酸酶同二聚和异二聚中的跨膜相互作用。
DOI：
10.1007/978-1-0716-3569-8_13
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Thévenin,Damien
中科院分区：
文献类型：
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作者：
Rizzo,Sophie;Thévenin,Damien
受体蛋白酪氨酸磷酸酶（RPTPs）是受体酪氨酸激酶（RTK）的关键调节因子之一，因此在调节信号转导中起关键作用。虽然RTKs的结构-功能关系已被广泛研究，但RPTPs活性的调节机制仍需充分了解。另一方面，同源二聚化已被证明拮抗RPTP催化活性，似乎是整个家族的一般特征。相反，它们与RTK物理相互作用的记录能力是它们对RTK的负调节不可或缺的，但有一个尚未提出的共同模型。然而，特定的跨膜（TM）结构域的相互作用和残基已被证明是必不可少的调节RPTP同源二聚化，与RTK底物的相互作用，和活动。因此，阐明TM结构域在RPTP调节中的贡献可以为这些受体如何发挥功能、相互作用并最终被调节提供重要的见解。本章介绍了显性负AraC为基础的转录报告（DN-AraTM）测定，以确定特定的TM相互作用的同源二聚化和异源关联与其他膜受体，如RTK。
Receptor protein tyrosine phosphatases (RPTPs) are one of the key regulators of receptor tyrosine kinases (RTKs) and therefore play a critical role in modulating signal transduction. While the structure–function relationship of RTKs has been widely studied, the mechanisms modulating the activity of RPTPs still need to be fully understood. On the other hand, homodimerization has been shown to antagonize RPTP catalytic activity and appears to be a general feature of the entire family. Conversely, their documented ability to physically interact with RTKs is integral to their negative regulation of RTKs, but there is a yet-to-be proposed common model. However, specific transmembrane (TM) domain interactions and residues have been shown to be essential in regulating RPTP homodimerization, interactions with RTK substrates, and activity. Therefore, elucidating the contribution of the TM domains in RPTP regulation can provide significant insights into how these receptors function, interact, and eventually be modulated. This chapter describes the dominant-negative AraC-based transcriptional reporter (DN-AraTM) assay to identify specific TM interactions essential to homodimerization and heteroassociation with other membrane receptors, such as RTKs.