| Research Abstract |
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
|
