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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rezaie, A. Articles by Esmon, C. Search for Related Content PubMed PubMed Citation Articles by Rezaie, A. Articles by Esmon, C. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Proline at the P2 position in protein C is important for calcium- mediated regulation of protein C activation and secretion AR Rezaie and CT Esmon Department of Pathology, University of Oklahoma Health Sciences Center, Howard Hughes Medical Institute, Oklahoma City. Protein C is a vitamin K-dependent plasma serine protease zymogen, which upon activation, functions as an anticoagulant. Protein C activation is catalyzed by a complex of thrombin (T) with thrombomodulin (TM). This activation is Ca(2+)-dependent, but Ca2+ inhibits protein C activation by thrombin alone. In most proteases, specificity is determined primarily by the residues that lie near the scissile bond. In protein C, the P2 position is Pro, whereas in the fibrinogen A chain, P2 is Val. We have expressed a Pro-->Val mutant of protein C (P168V) in mammalian cells. At saturating Ca2+, the P168V and wild-type proteins were activated by the T-TM complex equivalently, but half maximal rates of activation were obtained at 50 mumol/L Ca2+ for wild type and approximately 5 mmol/L Ca2+ for the P168V mutant. In the absence of TM, Ca2+ no longer inhibited the activation of the P168V mutant. These results indicate that Pro168 influences the Ca(2+)- dependent conformational changes in protein C that control activation. Recently, a patient with thrombotic complications has been identified with a Pro168-->Leu substitution. Both the P168V and the P168L mutation lead to impaired secretion caused by retention within the cell. Volume 83, Issue 9, pp. 2526-2531, 05/01/1994 Copyright © 1994 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Yang, S. Prasad, E. Di Cera, and A. R. Rezaie The Conformation of the Activation Peptide of Protein C Is Influenced by Ca2+ and Na+ Binding J. Biol. Chem., September 10, 2004; 279(37): 38519 - 38524. [Abstract] [Full Text] [PDF]

	Copyright © 1994 by American Society of Hematology         Online ISSN: 1528-0020