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Blood, 16 April 2009, Vol. 113, No. 16, pp. 3857-3864. Prepublished online as a Blood First Edition Paper on February 2, 2009; DOI 10.1182/blood-2008-07-171884. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-07-171884v1 113/16/3857    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Souri, M. Articles by Ichinose, A. Search for Related Content PubMed PubMed Citation Articles by Souri, M. Articles by Ichinose, A. Related Collections Thrombosis and Hemostasis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS Unique secretion mode of human protein Z: its Gla domain is responsible for inefficient, vitamin K–dependent and warfarin-sensitive secretion Masayoshi Souri1, Hiroki Iwata1, Wei Guang Zhang1, and Akitada Ichinose1 1 Department of Molecular Patho-Biochemistry and Patho-Biology of Blood Circulation, Yamagata University School of Medicine, Yamagata, Japan Protein Z is a vitamin K–dependent plasma glycoprotein that is involved in the regulation of blood coagulation. Plasma concentrations of protein Z vary widely between subjects and are greatly reduced during warfarin therapy. We developed a sensitive and quantitative assay for protein secretion using a secretory luciferase to explore the mode of secretion of protein Z compared with that of factor X. Protein Z secretion was much less efficient than factor X and was totally dependent upon added vitamin K, while factor X secretion was not. Protein Z secretion was highly sensitive to warfarin treatment of the synthesizing cells. In contrast, although factor X secretion was not precluded by warfarin, its -carboxylation was completely blocked. An exchange of the propeptide and/or -carboxyglutamic acid domain between protein Z and factor X reproduced the inefficient and warfarin-sensitive secretion pattern of protein Z, and vice versa. Joining of the propeptide and -carboxyglutamic acid domain to luciferase also demonstrated that the -carboxyglutamic acid domain of protein Z was responsible for its warfarin-sensitive secretion. Thus, it was concluded that the difference observed in secretion patterns of protein Z and factor X was mainly based on the structure of their -carboxyglutamic acid domains. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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