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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4561-4568. Prepublished online as a Blood First Edition Paper on February 17, 2005; DOI 10.1182/blood-2004-12-4618. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-12-4618v1 105/12/4561    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Davis, D. A. Articles by Tosato, G. Search for Related Content PubMed PubMed Citation Articles by Davis, D. A. Articles by Tosato, G. Related Collections Immunobiology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES Identification of carboxypeptidase N as an enzyme responsible for C-terminal cleavage of stromal cell-derived factor-1 in the circulation David A. Davis, Kathleen E. Singer, Maria De La Luz Sierra, Masashi Narazaki, Fuquan Yang, Henry M. Fales, Robert Yarchoan, and Giovanna Tosato From the HIV and AIDS Malignancy Branch, the Experimental Transplantation and Immunology Branch, National Cancer Institute, and the Laboratory of Biophysical Chemistry, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD. The chemokine stromal-derived factor-1 (SDF-1) is an essential regulator of hematopoiesis, lymphocyte homing, pre-B-cell growth, and angiogenesis. As SDF-1 is constitutively expressed in many tissues, chemokine function is mostly regulated by proteolytic degradation. Human serum cleaves the 68-amino acid chemokine, SDF-1, at both termini. The enzyme or enzymes responsible for the removal of the carboxy-terminal lysine from SDF-1, leading to significant reduction in biologic activity, have not been identified. Using a new biochemical assay for measuring the carboxy-terminal cleavage activity, we purified from serum and plasma a peptidase that specifically removes the carboxy-terminal lysine from SDF-1 and identified it as carboxypeptidase N (CPN, also known as kininase I, arginine carboxypeptidase, and anaphylotoxin inactivator). We demonstrate that SDF-1 in serum and plasma lacks the carboxy terminal lysine, and depletion of CPN from serum and plasma significantly reduces the SDF-1 carboxypeptidase activity. Purified CPN effectively and specifically removes the carboxy-terminal lysine from SDF-1 and significantly reduces the chemokine's biologic activity as a pre-B-cell growth factor and chemoattractant. Thus, in addition to its role as a regulator of the biologic activity of kinins and anaphylatoxins, CPN is an important regulator of the biologic activity of SDF-1 by reducing the chemokine-specific activity. (Blood. 2005;105:4561-4568) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X.-Y. Du and L. L.K. Leung Proteolytic regulatory mechanism of chemerin bioactivity Acta Biochim Biophys Sin, November 12, 2009; (2009) gmp091v1. [Abstract] [Full Text] [PDF] S. L. Mueller-Ortiz, D. Wang, J. E. Morales, L. Li, J.-Y. Chang, and R. A. Wetsel Targeted Disruption of the Gene Encoding the Murine Small Subunit of Carboxypeptidase N (CPN1) Causes Susceptibility to C5a Anaphylatoxin-Mediated Shock J. Immunol., May 15, 2009; 182(10): 6533 - 6539. [Abstract] [Full Text] [PDF] S. Struyf, S. Noppen, T. Loos, A. Mortier, M. Gouwy, H. Verbeke, D. Huskens, S. Luangsay, M. Parmentier, K. Geboes, et al. 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