Department of Experimental Neuroscience, IRCCS Fondazione Santa Lucia, 00143 Rome, Italy.
Department of Systems Medicine, Università di Roma "Tor Vergata", 00133 Rome, Italy.
Int J Mol Sci. 2020 Oct 24;21(21):7913. doi: 10.3390/ijms21217913.
It is well-appreciated that phosphorylation is an essential post-translational mechanism of regulation for several proteins, including group 1 metabotropic glutamate receptors (mGluRI), mGluR1, and mGluR5 subtypes. While contributions of various serine/threonine protein kinases on mGluRI modulation have been recognized, the functional role of tyrosine kinases (TKs) is less acknowledged. Here, while describing current evidence supporting that mGluRI are targets of TKs, we mainly focus on the modulatory roles of the ErbB tyrosine kinases receptors-activated by the neurotrophic factors neuregulins (NRGs)-on mGluRI function. Available evidence suggests that mGluRI activity is tightly dependent on ErbB signaling, and that ErbB's modulation profoundly influences mGluRI-dependent effects on neurotransmission, neuronal excitability, synaptic plasticity, and learning and memory processes.
人们普遍认为,磷酸化是几种蛋白质(包括第一组代谢型谷氨酸受体(mGluRI)、mGluR1 和 mGluR5 亚型)的一种重要的翻译后调节机制。虽然已经认识到各种丝氨酸/苏氨酸蛋白激酶对 mGluRI 调节的贡献,但酪氨酸激酶(TKs)的功能作用则较少被认可。在这里,在描述支持 mGluRI 是 TK 靶点的现有证据时,我们主要关注神经营养因子神经调节蛋白(NRGs)激活的 ErbB 酪氨酸激酶受体对 mGluRI 功能的调节作用。现有证据表明,mGluRI 的活性严格依赖于 ErbB 信号,而 ErbB 的调节深刻影响 mGluRI 对神经传递、神经元兴奋性、突触可塑性以及学习和记忆过程的影响。