Rosalind and Morris Goodman Cancer Centre and Departments of Biochemistry and Oncology, McGill University, Montreal, Quebec, Canada.
Trends Cell Biol. 2010 Nov;20(11):672-9. doi: 10.1016/j.tcb.2010.08.013. Epub 2010 Sep 23.
Receptor tyrosine kinases (RTKs) control the cellular response to a range of stimuli by binding extracellular factors and transmitting appropriate signals to intracellular sites. Protein tyrosine phosphatase 1B (PTP1B) modulates the activity of several RTKs by directly targeting the phosphorylated tyrosine residues that dictate their signaling output. Interestingly, the phenotypes of PTP1B deficiency in different contexts point to a more complex role in regulating RTK signaling. Exciting recent results indicate that the endocytic down-regulation of RTKs could be directly controlled by PTP1B. Microscopy studies have demonstrated an effect of PTP1B on post-endocytic internalization of RTKs into multivesicular bodies, and specific substrates that could influence their endosomal trafficking have been identified. These findings reveal a novel link between two important mechanisms of RTK signal attenuation and highlight the multifaceted impact of PTP1B on cell signaling.
受体酪氨酸激酶 (RTKs) 通过结合细胞外因子并将适当的信号传递到细胞内位点来控制细胞对一系列刺激的反应。蛋白酪氨酸磷酸酶 1B (PTP1B) 通过直接靶向决定其信号输出的磷酸化酪氨酸残基来调节几种 RTKs 的活性。有趣的是，不同背景下 PTP1B 缺乏的表型表明其在调节 RTK 信号方面具有更复杂的作用。令人兴奋的最新结果表明，RTKs 的内吞下调可能直接受到 PTP1B 的控制。显微镜研究表明 PTP1B 对 RTKs 进入多泡体的内吞后内化有影响，并且已经确定了可能影响其内体运输的特定底物。这些发现揭示了 RTK 信号衰减的两个重要机制之间的新联系，并强调了 PTP1B 对细胞信号的多方面影响。
