Elucidation of Functional Implication of Post-translational Tyrosine Suifation

翻译后蛋白质修饰酪氨酸硫酸化是目前已知有广泛的发生在蛋白质的多细胞真核生物。鉴于目前发现的酪氨酸硫酸化（TyrS）蛋白绝大多数是分泌型蛋白，而催化蛋白酪氨酸硫酸化反应的酪氨酸蛋白磺基转移酶（TPST）位于高尔基体，对这种独特的蛋白修饰的功能相关性的初步推测主要集中在蛋白分泌方面。进一步阐述了酪氨酸硫酸化在分泌蛋白包装成分泌颗粒中的假设作用。沿着相同的路线，我们一直在研究参与介导酪氨酸硫酸化蛋白的靶向和/或细胞内转运的推定TyrS受体的存在。采用亲和凝胶电泳技术，我们在小鼠的胆酸钠提取物中检测到一个175 kDa的酪氨酸-O-硫酸盐结合蛋白。 ...更多信息 牛肝脏和胰腺以及犬肝脏和胰腺的微粒体膜部分。蛋白质印迹分析揭示了牛肝酪氨酸结合蛋白在体内和体外与酪氨酸硫酸化蛋白复合物中的存在，表明前者是后者的受体的推定作用。1.in一个假设的模型TyrS残基作为一个顶端的靶向信号，在生物合成的酪氨酸硫酸蛋白质的运输过程中，介导的TyrS受体，在MDCK细胞提出。TyrS蛋白被TyrS受体识别并结合，并包装到从反式高尔基体膜隔室出芽的转运囊泡中。转运囊泡与卷曲样膜室融合，其中酪氨酸硫酸化蛋白由于推测通过ATP酶/H+泵的作用产生的低pH环境而与TyrS受体解离。携带游离TyrS蛋白的囊泡从卷曲样膜隔室出芽并向质膜的顶端结构域迁移。在与顶端质膜融合后，酪氨酸硫酸化蛋白从顶端表面分泌。少

Post-translational protein modification by tyrosine sulfation is now known to have a widespread occurrence among proteins of multicellular eukaiyotic organisms. I view of that the vast majority of tyrosine-sulfated (TyrS) proteins identified are secretory proteins and that the tyrosyiprotein sulfotransferase (TPST), which catalyzes the protein tyrosine sulfation reaction, is located in the Golgi, the initial speculation on the functional relevance of this unique protein modification was focused on the aspect of protein secretion. A hypothetical role of tyrosine sulfation in the packaging of secretory proteins into secretory granules was further elaborated. Along the same line, we have been investigating the presence of a putative TyrS receptor involved in mediating the targeting and/or intracellular transport of tyrosine-sulfated proteins. By employing the affinity gel fraction technique, we have detected a 175 kDa tyrosine-O-.sulfate-binding protein in sodium choleate etracts of the m … More icrosomal membrane fractions of bovine liver and pancreas, as well as canine liver and pancreas. Western blot analysis revealed the presence of the bovine liver TyrS-binding protein in complexes with tyrosine-sulfated proteins both 1.in vivo and in vitro, suggesting the putative role of the former being the receptor for the latter. A hypothetical model for TyrS residues serving as an apical targeting signal during the biosynthetic transport of tyrosine-sulfated proteins, as mediated by the TyrS receptor, in MDCK cells is proposed. TyrS proteins are recognized and bound by the TyrS receptor, and packaged into the transport vesicle budded off from the trans Golgi membrane compartment. The transport vesicle fuses with a CURL-like membrane compartment in which tyrosine-sulfated proteins become dissociated from the TyrS receptor due to the low pH environment presumably generated through the action of ATPase/H+ pump. The vesicle carrying free TyrS proteins buds off from the CURl-like membrane compartment and migrates toward the apical domain of the plasma membrane. Upon fusion with the apical plasma membrane, tyrosine-sulfated proteins become secreted from the apical surface. Less