Elucidation of Functional Implication of Post-translational Tyrosine Suifation

酪氨酸磺化的翻译后蛋白修饰在多细胞真海生物的蛋白质中广泛存在。鉴于鉴定出的绝大多数酪氨酸-硫酸化（TyrS）蛋白都是分泌蛋白，而催化酪氨酸-硫酸化反应的酪氨酸蛋白硫转移酶（TPST）位于高尔基体中，对这一独特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磺化在将分泌蛋白包装成分泌颗粒中的假设作用。沿着同样的思路，我们一直在研究一种假定的TyrS受体的存在，该受体参与介导酪氨酸磺酸蛋白的靶向和/或细胞内运输。通过亲和凝胶分离技术，我们检测到一个175 kDa的酪氨酸- o -。牛肝脏和胰腺以及犬肝脏和胰腺的更多微粒体膜组分的胆酸钠提取物中的硫酸盐结合蛋白。Western blot分析显示，牛肝脏tyrs结合蛋白与酪氨酸-硫酸化蛋白(1。在体内和体外，表明前者的假定作用是后者的受体。本文提出了一个假设模型，在MDCK细胞中TyrS受体介导的酪氨酸磺酸蛋白的生物合成运输过程中，TyrS残基作为顶端靶向信号。TyrS蛋白被TyrS受体识别和结合，并被包装到从反式高尔基膜室分离出来的运输囊泡中。运输囊泡与卷曲样膜室融合，其中酪氨酸-硫酸盐化蛋白由于可能通过atp酶/H+泵的作用产生的低pH环境而与TyrS受体分离。携带自由的TyrS蛋白的囊泡从卷曲状的膜室中萌发并向质膜的顶端区域迁移。在与根尖质膜融合后，酪氨酸磺酸蛋白从根尖表面分泌出来。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