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This Article Full Text Full Text (PDF) 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Katsumi, A. Articles by Saito, H. Search for Related Content PubMed PubMed Citation Articles by Katsumi, A. Articles by Saito, H. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  The Carboxyl-Terminal Region of Protein C Is Essential for Its Secretion Akira Katsumi, Tetsuhito Kojima, Takao Senda, Tomio Yamazaki, Hiroaki Tsukamoto, Isamu Sugiura, Shigeru Kobayashi, Toshiyuki Miyata, Hideaki Umeyama, and Hidehiko Saito From the First Department of Internal Medicine and the First Department of Anatomy, Nagoya University School of Medicine, Nagoya, Japan; the School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan; the Laboratory of Thrombosis Research, National Cardiovascular Center Research Institute, Suita, Japan; and the Aichi Blood Disease Research Foundation, Nagoya, Japan. We have previously reported a mutated protein C, designated protein C Nagoya (PCN), characterized by the deletion of a single guanine residue (8857G). This frameshift mutation results in the replacement of the carboxyl-terminal 39 amino acids of wild-type protein C (G381-P419) by 81 abnormal amino acids. This elongated mutant was not effectively secreted, and was retained in the endoplasmic reticulum. To determine why PCN is not secreted, we constructed a series of mutants from which some or all of the 81 amino acids were deleted. None of these shortened proteins were secreted from producing cells, indicating that the carboxyl-terminal extension is not mainly responsible for the intracellular retention of PCN, and that the 39 carboxyl-terminal amino acids of wild-type protein C are required for secretion. To determine which residues are essential for the secretion of protein C, deletion mutants of the carboxyl-terminal region (D401-P419) were prepared. Metabolic labeling showed that mutants of protein C truncated before W417, Q414, E411, or K410 were efficiently secreted. On the other hand, the mutants truncated before D409 were retained and degraded intracellularly. Immunofluorescence and immunoelectron microscopy showed that truncation before D409 blocks the movement from rough endoplasmic reticulum to the Golgi apparatus. To understand the conformational change in the carboxyl-terminal region, two models of truncated activated protein C were constructed using energy optimization and molecular dynamics with water molecules. Blood, Vol. 91 No. 10 (May 15), 1998: pp. 3784-3791 © 1998 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: Y. Espinosa-Parrilla, T. Yamazaki, N. Sala, B. Dahlback, and P. G. de Frutos Protein S secretion differences of missense mutants account for phenotypic heterogeneity Blood, January 1, 2000; 95(1): 173 - 179. [Abstract] [Full Text] [PDF]

	Copyright © 1998 by American Society of Hematology         Online ISSN: 1528-0020