The phosphorylation of the two-chain form of vitronectin by protein kinase A is heparin dependent.
In circulating blood, vitronectin occurs in two forms: a single-chain (75 kDa) and an endogenously clipped two-chain form (65 kDa and 10 kDa) held together by a disulfide bridge. The 75 kDa form was previously shown to be phosphorylated at Ser378 by protein kinase A, released by physiologically stimulated platelets. By contrast, at pH 7.5 the two-chain form is not phosphorylated at all. Heparin or heparan sulfate are shown here to modulate the conformation of clipped vitronectin at physiological pH, exposing Ser378 and allowing its stoichiometric phosphorylation by the kinase. At this pH the two-chain form of vitronectin in plasma exhibits a higher affinity for heparin, and behaves as a flexible molecule, which can conformationally respond to heparin and heparan sulfate, effectors involved in vitronectin function.
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
D
D
Chain
B
B
Korc-Grodzicki
T
T
Kreizman
S
S
Shaltiel
D000595:Amino Acid Sequence; D006023:Glycoproteins / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000494:pharmacology; D006493:Heparin / Q000502:physiology*; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011494:Protein Kinases / Q000378:metabolism*; D019096:Vitronectin
D006023:Glycoproteins; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D046911:Macromolecular Substances; D010768:Phosphoserine; D011494:Protein Kinases; D019096:Vitronectin