Association of protein-tyrosine phosphatase PTP-BAS with the transcription-factor-inhibitory protein IkappaBalpha through interaction between the PDZ1 domain and ankyrin repeats.
Association of protein-tyrosine phosphatase PTP-BAS with the transcription-factor-inhibitory protein IkappaBalpha through interaction between the PDZ1 domain and ankyrin repeats.
复制标题
蛋白酪氨酸磷酸酶 PTP-BAS 通过 PDZ1 结构域和锚蛋白重复序列之间的相互作用与转录因子抑制蛋白 IkappaBalpha 关联。
作者：
Kazuhiko Maekawa;Noriko Imagawa;Akira Naito;Shigenori Harada;Osamu Yoshie;Shin Takagi
PTP-BAS是一种膜相关蛋白酪氨酸磷酸酶，含有一个4.1带同源区和5个PDZ (PSD-95 Dlg ZO-1)[碟状大同源区('DHR')/Gly-Leu-Gly-Phe ('GLGF')]结构域。据报道，第二和第四个PDZ结构域与Fas/CD95相关。利用第一个PDZ结构域作为诱饵进行酵母双杂交筛选，鉴定出IkappaBalpha为结合蛋白。IkappaBalpha通过n端三个锚蛋白重复序列的延伸与PDZ1结合。通过共免疫沉淀实验，这种关联也在HeLa细胞中得到证实。通过表达PTP-BAS显性阴性突变体抑制PTP-BAS，导致IkappaBalpha酪氨酸磷酸化。酪氨酸磷酸化ikappabα是再氧化过程中核因子(NF)-kappaB活化的关键事件。因此，PTP-BAS可能在高氧化应激下对NF-kappaB的激活起调节作用。
PTP-BAS is a membrane-associated protein tyrosine phosphatase containing a band-4.1 homology region and five PDZ (PSD-95 Dlg ZO-1) [discs-large homology region ('DHR')/Gly-Leu-Gly-Phe ('GLGF')] domains. The second and fourth PDZ domains were reported to associate with Fas/CD95. By using the first PDZ domain as a bait in yeast two-hybrid screening, we have identified IkappaBalpha as a binding protein. IkappaBalpha associated with PDZ1 through the stretch of the N-terminal three ankyrin repeats. The association was also confirmed in HeLa cells by co-immunoprecipitation experiments. Inhibition of PTP-BAS by expression of dominant-negative PTP-BAS mutant resulted in tyrosine-phosphorylation of IkappaBalpha. Tyrosine-phosphorylation of IkappaBalpha is a key event in activation of nuclear factor (NF)-kappaB during reoxygenation. PTP-BAS may thus play a regulatory role in activation of NF-kappaB under high oxidative stress.