Tyrosine phosphorylation and regulation of the AMPA receptor by Src family tyrosine kinases
Tyrosine phosphorylation and regulation of the AMPA receptor by Src family tyrosine kinases
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DOI：
10.1523/jneurosci.0799-04.2004
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发表时间：
2004-07-07
影响因子：
5.3
通讯作者：
Huganir, RL
中科院分区：
文献类型：
--
作者：
Hayashi, T;Huganir, RL
AMPA受体的磷酸化是受体功能调节的主要机制，是中枢神经系统突触可塑性的几种形式的基础。虽然AMPA受体的丝氨酸和苏氨酸的磷酸化已经得到了很好的研究，但AMPA受体的酪氨酸磷酸化的潜在作用还没有被研究过。在这里，我们证明了AMPA受体的GluR2亚单位在体外和体内都被其C末端附近的酪氨酸876上的Src家族酪氨酸激酶所磷酸化。此外，Glur激动剂对培养的皮质神经元的处理增加了酪氨酸876的磷酸化。GluR2的酪氨酸磷酸化降低了与GluR2相互作用分子GRIP1/2的结合，而不影响PICK1的相互作用。此外，酪氨酸876的突变消除了AMPA和NMDA诱导的GluR2亚基的内化。这些数据表明，由Src家族酪氨酸激酶激活的GluR2 C末端酪氨酸876的酪氨酸磷酸化对AMPA受体功能的调节很重要，对突触的可塑性可能也很重要。
Phosphorylation of AMPA receptors is a major mechanism for the regulation of receptor function and underlies several forms of synaptic plasticity in the CNS. Although serine and threonine phosphorylation of AMPA receptors has been well studied, the potential role of tyrosine phosphorylation of AMPA receptors has not been investigated. Here, we show that the GluR2 subunit of AMPA receptors is tyrosine phosphorylated in vitro and in vivo by Src family tyrosine kinases on tyrosine 876 near its C terminus. In addition, GluR agonist treatment of cultured cortical neurons increased phosphorylation of tyrosine 876. The association with GluR2-interacting molecules GRIP1/2 was decreased by tyrosine phosphorylation of GluR2, whereas PICK1 interaction was not influenced. Moreover, mutation of tyrosine 876 eliminated AMPA- and NMDA-induced internalization of the GluR2 subunit. These data indicate that tyrosine phosphorylation of tyrosine 876 on the GluR2 C terminus by Src family tyrosine kinases is important for the regulation of AMPA receptor function and may be important for synaptic plasticity.