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

J. Biol. Chem., Vol. 280, Issue 49, 40867-40874, December 9, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/49/40867    most recent M505679200v1 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 Meidan, R. Articles by Levy, N. Search for Related Content PubMed PubMed Citation Articles by Meidan, R. Articles by Levy, N. Social Bookmarking                      What's this?

Endothelin-converting Enzyme-1, Abundance of Isoforms a-d and Identification of a Novel Alternatively Spliced Variant Lacking a Transmembrane Domain^*

Rina Meidan1, Eyal Klipper, Tamar Gilboa, Laurent Muller, and Nitzan Levy

From the Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel and the INSERM U 36, College de France (Paris), 75005 Paris, France

Endothelin-converting enzyme-1 (ECE-1) cleaves big endothelins, as well as bradykinin and -amyloid peptide. Several isoforms of ECE-1 (a-d) have been identified to date; they differ only in their NH₂ terminus but share the catalytic domain located in the COOH-terminal end. Using quantitative PCR, we found ECE-1d to be the most abundant type in several endothelial cells (EC) types. In addition to full-length ECE-1 forms we have identified novel, alternatively spliced mRNAs of ECE-1 b-d. These splice variants (SVs) lack exon 3', which codes for the transmembrane region and is present in full-length forms. SVs mRNA were highly expressed in EC derived from macro and microvascular beds but much less so in other, non-endothelial cells expressing ECE-1, which suggests that the splicing mechanism is cell-specific. Analyses of ECE-1d and its SV form in stably transfected HEK-293 cells revealed that both proteins were recognized by anti COOH-terminal ECE-1 antibodies, but anti NH₂-terminal antibodies only bound ECE-1d. The novel protein, designated ECE-1 sv, has an apparent molecular mass of 75 kDa; by using site-directed mutagenesis its start site was identified in a region common to all ECE-1 forms suggesting that ECE-1 b-d SV mRNAs are translated into the same protein. In agreement with the findings demonstrating common COOH terminus for ECE-1sv and ECE-1d, both exhibited a similar catalytic activity. However, immunofluorescence staining and differential centrifugation revealed a distinct intracellular localization for these two proteins. The presence of ECE-1sv in different cellular compartments than full-length forms of the enzyme may suggest a distinct physiological role for these proteins.

Received for publication, May 24, 2005 , and in revised form, September 7, 2005.

^* This work was supported by a grant from the Israel Science Foundation (ISF 0396189). 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.

¹ To whom correspondence should be addressed. Tel.: 972-89489394; Fax: 972-89465763; E-mail: rina.meidan{at}huji.ac.il.

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

This article has been cited by other articles:

				M. Khamaisi, R. Dahan, S. Hamed, Z. Abassi, S. N. Heyman, and I. Raz Role of Protein Kinase C in the Expression of Endothelin Converting Enzyme-1 Endocrinology, March 1, 2009; 150(3): 1440 - 1449. [Abstract] [Full Text] [PDF]

				O. Rayhman, E. Klipper, L. Muller, B. Davidson, R. Reich, and R. Meidan Small Interfering RNA Molecules Targeting Endothelin-Converting Enzyme-1 Inhibit Endothelin-1 Synthesis and the Invasive Phenotype of Ovarian Carcinoma Cells Cancer Res., November 15, 2008; 68(22): 9265 - 9273. [Abstract] [Full Text] [PDF]

				A. Iwase, H. Ando, T. Nagasaka, M. Goto, T. Harata, and F. Kikkawa Distribution of Endothelin-converting Enzyme-1 and Neutral Endopeptidase in Human Endometrium J. Histochem. Cytochem., December 1, 2007; 55(12): 1229 - 1235. [Abstract] [Full Text] [PDF]