Alfalah, Marwan and Parkin, Edward T. and Jacob, Ralf and Sturrock, Edward D. and Mentele, Reinhard and Turner, Anthony J. and Hooper, Nigel M. and Naim, Hassan Y. (2001) A Point Mutation in the Juxtamembrane Stalk of Human Angiotensin I-converting Enzyme Invokes the Action of a Distinct Secretase. Journal of Biological Chemistry, 276 (24). pp. 21105-21109.
Full text not available from this repository.Abstract
Angiotensin I-converting enzyme (ACE) is one of a number of integral membrane proteins that is proteolytically shed from the cell surface by a zinc metallosecretase. Mutagenesis of Asn631 to Gln in the juxtamembrane stalk region of ACE resulted in more efficient secretion of the mutant protein (ACENQ) as determined by pulse-chase analysis. In contrast to the wild-type ACE, the cleavage of ACENQ was not blocked by the metallosecretase inhibitor batimastat but by the serine protease inhibitor, 1,3-dichloroisocoumarin. Incubation of the cells at 15 °C revealed that ACENQ was cleaved in the endoplasmic reticulum, and mass spectrometric analysis of the secreted form of the protein indicated that it had been cleaved at the Asn635-Ser636 bond, three residues N-terminal to the normal secretase cleavage site at Arg638-Ser639. These data clearly show that a point mutation in the juxtamembrane region of an integral membrane protein can invoke the action of a mechanistically and spatially distinct secretase. In light of this observation, previous data on the effect of mutations in the juxtamembrane stalk of shed proteins being accommodated by a single secretase having a relaxed specificity need to be re-evaluated.
| Item Type: | Article |
|---|---|
| Journal or Publication Title: | Journal of Biological Chemistry |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| Departments: | Faculty of Health and Medicine > Biomedical & Life Sciences |
| ID Code: | 9454 |
| Deposited By: | Dr Edward Parkin |
| Deposited On: | 11 Jun 2008 10:30 |
| Refereed?: | Yes |
| Published?: | Published |
| Last Modified: | 26 Jul 2012 18:37 |
| Identification Number: | |
| URI: | http://eprints.lancs.ac.uk/id/eprint/9454 |
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