HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 41, 43052-43060, October 8, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/41/43052    most recent M407180200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wajih, N. Articles by Wallin, R. Search for Related Content PubMed PubMed Citation Articles by Wajih, N. Articles by Wallin, R. Social Bookmarking                      What's this?

Processing and Transport of Matrix -Carboxyglutamic Acid Protein and Bone Morphogenetic Protein-2 in Cultured Human Vascular Smooth Muscle Cells

EVIDENCE FOR AN UPTAKE MECHANISM FOR SERUM FETUIN^*

Nadeem Wajih, Terete Borras, Wei Xue, Susan M. Hutson¶, and Reidar Wallin||

From the Departments of Internal Medicine and ^¶Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27517 and the Department of Ophthalmology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599

Matrix -carboxyglutamic acid protein (MGP) is a member of the vitamin K-dependent protein family with unique structural and physical properties. MGP has been shown to be an inhibitor of arterial wall and cartilage calcification. One inhibitory mechanism is thought to be binding of bone morphogenetic protein-2. Binding has been shown to be dependent upon the vitamin K-dependent -carboxylation modification of MGP. Since MGP is an insoluble matrix protein, this work has focused on intracellular processing and transport of MGP to become an extracellular binding protein for bone morphogenetic protein-2. Human vascular smooth muscle cells (VSMCs) were infected with an adenovirus carrying the MGP construct, which produced non--carboxylated MGP and fully -carboxylated MGP. Both forms of MGP were found in the cytosolic and microsomal fractions obtained from the cells by differential centrifugation. The crude microsomal fraction was shown to contain an additional, more acidic Ser-phosphorylated form of MGP believed to be the product of Golgi casein kinase. The data suggest that phosphorylation of MGP dictates different transport routes for MGP in VSMCs. A proteomic approach failed to identify a larger soluble precursor of MGP or an intracellular carrier protein for MGP. Evidence is presented for a receptor-mediated uptake mechanism for fetuin by cultured human VSMCs. Fetuin, shown by mass spectrometry not to contain MGP, was found to be recognized by anti-MGP antibodies. Fetuin uptake and secretion by proliferating and differentiating cells at sites of calcification in the arterial wall may represent an additional protective mechanism against arterial calcification.

Received for publication, June 25, 2004 , and in revised form, July 26, 2004.

^* This work was supported by National Institutes of Health Grant RO1HL069331 (to R. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Dept. of Internal Medicine, Section on Rheumatology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157. Tel.: 336-716-6166; Fax: 336-716-9821; E-mail: rwallin{at}wfubmc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. J. H. van Summeren, W. G. M. Spliet, A. van Royen-Kerkhof, C. Vermeer, M. Lilien, W. Kuis, and L. J. Schurgers Calcinosis in juvenile dermatomyositis: a possible role for the vitamin K-dependent protein matrix Gla protein Rheumatology, March 1, 2008; 47(3): 267 - 271. [Abstract] [Full Text] [PDF]

				K. D. Hadfield, C. F. Rock, C. A. Inkson, S. L. Dallas, L. Sudre, G. A. Wallis, R. P. Boot-Handford, and A. E. Canfield HtrA1 Inhibits Mineral Deposition by Osteoblasts: REQUIREMENT FOR THE PROTEASE AND PDZ DOMAINS J. Biol. Chem., February 29, 2008; 283(9): 5928 - 5938. [Abstract] [Full Text] [PDF]

				N. Wajih, S. M Hutson, and R. Wallin Disulfide-dependent Protein Folding Is Linked to Operation of the Vitamin K Cycle in the Endoplasmic Reticulum: A PROTEIN DISULFIDE ISOMERASE-VKORC1 REDOX ENZYME COMPLEX APPEARS TO BE RESPONSIBLE FOR VITAMIN K1 2,3-EPOXIDE REDUCTION J. Biol. Chem., January 26, 2007; 282(4): 2626 - 2635. [Abstract] [Full Text] [PDF]

				J. L. Reynolds, J. N. Skepper, R. McNair, T. Kasama, K. Gupta, P. L. Weissberg, W. Jahnen-Dechent, and C. M. Shanahan Multifunctional Roles for Serum Protein Fetuin-A in Inhibition of Human Vascular Smooth Muscle Cell Calcification J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2920 - 2930. [Abstract] [Full Text] [PDF]

				L. J. Schurgers, K. J.F. Teunissen, M. H.J. Knapen, M. Kwaijtaal, R. van Diest, A. Appels, C. P. Reutelingsperger, J. P.M. Cleutjens, and C. Vermeer Novel Conformation-Specific Antibodies Against Matrix {gamma}-Carboxyglutamic Acid (Gla) Protein: Undercarboxylated Matrix Gla Protein as Marker for Vascular Calcification Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1629 - 1633. [Abstract] [Full Text] [PDF]

				V. Laize, P. Martel, C. S. B. Viegas, P. A. Price, and M. L. Cancela Evolution of Matrix and Bone {gamma}-Carboxyglutamic Acid Proteins in Vertebrates J. Biol. Chem., July 22, 2005; 280(29): 26659 - 26668. [Abstract] [Full Text] [PDF]

				N. Wajih, D. C. Sane, S. M. Hutson, and R. Wallin Engineering of a Recombinant Vitamin K-dependent {gamma}-Carboxylation System with Enhanced {gamma}-Carboxyglutamic Acid Forming Capacity: EVIDENCE FOR A FUNCTIONAL CXXC REDOX CENTER IN THE SYSTEM J. Biol. Chem., March 18, 2005; 280(11): 10540 - 10547. [Abstract] [Full Text] [PDF]