Tyrosine phosphorylation of ErbB4 is enhanced by PSD95 and repressed by protein tyrosine phosphatase receptor type Z
Tyrosine phosphorylation of ErbB4 is enhanced by PSD95 and repressed by protein tyrosine phosphatase receptor type Z
复制标题
DOI：
10.1093/jb/mvm140
复制
发表时间：
2007-09-01
影响因子：
2.7
通讯作者：
Noda, Masaharu
中科院分区：
文献类型：
--
作者：
Fujikawa, Akihiro;Chow, Jeremy Pak Hong;Noda, Masaharu
蛋白酪氨酸磷酸酶受体Z型（Ptprz/PTP zeta/RPTP beta）是一种优先在脑中表达的受体样蛋白酪氨酸磷酸酶（RPTP）。ErbB 4是ErbB家族酪氨酸激酶的成员，被称为神经调节蛋白（NRG）受体。已知两者分别通过其羧基末端的PDZ结合基序在第二和第一/第二PDZ（PSD 95/DiseLarge/Diseoccludensl）结构域上结合突触后密度-95（PSD 95）。在这里，我们报告Ptprz和ErbB 4之间的功能相互作用。Ptprz的细胞内羧基末端区域从成年大鼠突触体制备物中拉下PSD 95和ErbB 4。ErbB 4和Ptprz共定位于前额叶皮层神经元的胞体和顶树突。在HEK 293 T细胞中，ErbB 4的磷酸化通过PSD 95的共表达而升高，其通过Ptprz的额外表达而被抑制。使用ErbB 4的整个细胞内区域（ICR）的体外实验也表明，PSD 95刺激ErbB 4的自磷酸化，并且Ptprz的ICR使ErbB 4去磷酸化，而不依赖于PSD 95的存在。结合Ptprz缺陷小鼠中ErbB 4酪氨酸磷酸化水平增加的发现，这些结果表明Ptprz在抑制成年脑中突触后密度处PSD 95对ErbB 4的自激活中具有作用。
Protein tyrosine phosphatase receptor type Z (Ptprz/PTP zeta/RPTP beta) is a receptor-like protein tyrosine phosphatase (RPTP) preferentially expressed in the brain. ErbB4 is a member of the ErbB-family tyrosine kinases known as a neuregulin (NRG) receptor. Both are known to bind to postsynaptic density-95 (PSD95) on the second and the first/second PDZ (PSD95/Dise large/zona occludensl) domains, respectively, through the PDZ-binding motif of their carboxyl termini. Here we report a functional interaction between Ptprz and ErbB4. An intraeellular carboxyl-terminal region of Ptprz pulled-down PSD95 and ErbB4 from an adult rat synaptosomal preparation. ErbB4 and Ptprz showed co-localization in cell bodies and apical dendrites of neurons in the prefrontal cortex. In HEK293T cells, phosphorylation of ErbB4 was raised by co-expression of PSD95, which was repressed by additional expression of Ptprz. In vitro experiments using the whole intracellular region (ICR) of ErbB4 also showed that PSD95 stimulates the autophosphorylation of ErbB4, and that the ICR of Ptprz dephosphorylates ErbB4 independent of the presence of PSD95. Taken together with the finding that the tyrosine phosphorylation level of ErbB4 was increased in Ptprz-deficient mice, these results suggest that Ptprz has a role in suppressing the autoactivation of ErbB4 by PSD95 at the postsynaptic density in the adult brain.