Tyrosine sulfation and the secretory pathway

Tyrosine sulfation is a widespread posttranslational modification. Most tyrosine-sulfated proteins identified so far are secretory, including several neuropeptides. Tyrosine sulfation occurs in the trans Golgi and is one of the last processing steps before proteins exit from the Golgi complex. The sulfation reaction is catalyzed by tyrosylprotein sulfotransferase, an integral membrane protein that recognizes tyrosine residues in exposed protein domains containing acidic amino acids. In the cases studied to date, tyrosine sulfation has been found to be irreversible, resulting in a life-long alteration in the phenotype of the secretory proteins. The biological role of tyrosine sulfation has so far been elucidated in only a few cases. The intracellular transport kinetics of a secretory protein and the biological activity of certain neuropeptides have been found to be affected by this modification. Future functional studies will be greatly facilitated by the use of chlorate, a sulfate analogue that has recently been found to be a potent and nontoxic inhibitor of sulfation in intact cells.