Details

Autor(en) / Beteiligte

• Hortin, Glen L.
• Farries, Timothy C.
• Graham, James P.
• Atkinson, John P.

Titel

Sulfation of Tyrosine Residues Increases Activity of the Fourth Component of Complement

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1989-02, Vol.86 (4), p.1338-1342

Ort / Verlag

Washington, DC: National Academy of Sciences of the United States of America

Erscheinungsjahr

1989

Quelle

MEDLINE

Beschreibungen/Notizen

• Sulfation of tyrosine residues recently has been recognized as a biosynthetic modification of many plasma proteins and other secretory proteins. Effects of this sitespecific modification on protein function are not known, but the activity of several peptides such as cholecystokinin is greatly augmented by sulfation. Here, we examine the role of sulfation in the processing and activity of C4 (the fourth component of complement), one of the few proteins in which sites and stoichiometry of tyrosine sulfation have been characterized. Our results, with C4 as a paradigm, suggest that sulfation of tyrosine residues can have major effects on the activity of proteins participating in protein-protein interactions. Sulfation of C4 synthesized by Hep G2 cells was blocked by incubating the cells with NaClO3 and guaiacol. These sulfation inhibitors did not alter secretion or other steps in the processing of C4. However, hemolytic activity of C4 was decreased more than 50%. The inhibitors' effect on C4 activity was prevented by adding Na2SO4 to restore sulfation of C4. Activity of C3, a complement component homologous to C4 but lacking tyrosine sulfate residues, was minimally reduced (19%) by the inhibitors. Decreased hemolytic activity of nonsulfated C4 apparently resulted from impaired interaction with complement subcomponent C$\overline{1\text{s}}$ (EC 3.4.21.42), the protease that physiologically activates C4. Purified C$\overline{1\text{s}}$ was able to cleave nonsulfated C4, but ≈ 10-fold higher concentrations of C$\overline{1\text{s}}$ were required for that cleavage than to yield equivalent cleavage of sulfated C4. Our results suggest that activation of C4, a central component in the classical pathway of complement activation, is influenced by the level of sulfation of the protein. Thus, sulfation of C4 provides a potential locus for physiological or pharmacological modulation of complement-mediated opsonization and inflammation.