Extracellular cysteines define ectopeptidase (APN, CD13) expression and function

Free Radical Biology & Medicine
Beate FirlaU Lendeckel

Abstract

Alanyl aminopeptidase (APN) is a surface-bound metallopeptidase that processes the N-terminals of biologically active peptides such as enkephalins, angiotensins, neurokinins, and cytokines. It exerts profound activity on vital processes such as immune response, cellular growth, and blood pressure control. Inhibition of either APN gene expression or its enzymatic activity severely affects leukocyte growth and function. We show here that oxidoreductase-mediated modulations of the cell surface thiol status affect the enzymatic activity of APN. Additional evidence for the pivotal role of extracellular cysteines in the APN molecule was obtained when substitution of any of these six cysteines caused complete loss of surface expression and enzymatic activity. In contrast, the transmembrane Cys24 appears to have no similar function. Enzymatically inactive cysteine mutants were retained in the endoplasmic reticulum as shown by high-resolution imaging and Endoglycosidase H digestion. In the absence of any crystal-structure data, the demonstration that individual extracellular cysteines contribute to APN expression and function appears to be of particular importance. The data are the first to show thiol-dependent modulation of the activit...Continue Reading

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Citations

Jun 22, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yi YangJoseph Loscalzo
Aug 2, 2002·Biochemical and Biophysical Research Communications·Alexander Navarrete SantosDagmar Riemann
Oct 11, 2005·Medicinal Research Reviews·Brigitte Bauvois, Daniel Dauzonne
Nov 8, 2016·International Journal of Cardiology·Tobias BecherKsenija Stach

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Methods Mentioned

BETA
Transfection
FCS
PCR
FACS
flow cytometry
glycosylation
fluorescence microscopy

Software Mentioned

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