Maturation of secreted meprin alpha during biosynthesis: role of the furin site and identification of the COOH-terminal amino acids of the mouse kidney metalloprotease subunit

Archives of Biochemistry and Biophysics
J Tang, Judith S Bond

Abstract

The alpha subunit of meprin A is synthesized as a type I integral membrane protein; however, the mature form contains no membrane-spanning region due to COOH-terminal proteolytic cleavage during biosynthesis. Previous studies with transfected mouse meprin alpha subunit cDNA, showed that the inserted (I) domain in the COOH-terminus was essential for proteolytic processing and transport of the subunit out of the endoplasmic reticulum. A furin site in the I domain was implicated as the site of cleavage in the rat meprin alpha subunit, however, this site was shown not to be required in the homologous mouse subunit. The present studies were designed to determine whether there is a species difference in the use of the furin site for processing of the subunit, and whether the different mutations used in the previous studies could account for the different conclusions regarding the importance of the furin site. When the furin sites in mouse and rat cDNAs were mutated, using similar amino acid substitutions, and expressed in human 293 cells, all mutants were secreted, and had comparable activities compared to the wild-types against a protein (azocasein) and peptide (bradykinin analog) substrate. These data revealed no difference between...Continue Reading

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Citations

Jul 31, 2003·The Journal of Biological Chemistry·James P VillaJudith S Bond
Nov 20, 2002·Biological Chemistry·Greg P BertenshawJudith S Bond
Feb 22, 2013·American Journal of Physiology. Renal Physiology·Gur P KaushalSudhir V Shah
Jul 27, 2010·Interdisciplinary Sciences, Computational Life Sciences·Chiung-Hui HungShinn-Ying Ho
Jan 27, 2015·Matrix Biology : Journal of the International Society for Matrix Biology·Johannes ProxChristoph Becker-Pauly
Feb 3, 2019·The Journal of Biological Chemistry·Judith S Bond
Apr 1, 2017·BMC Bioinformatics·Wei-Sheng TienKun-Pin Wu
Feb 3, 2016·Current Protocols in Protein Science·Sven FridrichWalter Stöcker
Oct 26, 2002·The Journal of Biological Chemistry·Greg P BertenshawJudith S Bond
Apr 22, 2005·The Journal of Biological Chemistry·Hideki TagawaShogo Oka
Nov 22, 2020·The Journal of Biological Chemistry·Judith S Bond
Jul 16, 1999·Biochemical and Biophysical Research Communications·W Jiang, B G Beatty

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