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A Point Mutation in the Juxtamembrane Stalk of Human Angiotensin I-converting Enzyme Invokes the Action of a Distinct Secretase.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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A Point Mutation in the Juxtamembrane Stalk of Human Angiotensin I-converting Enzyme Invokes the Action of a Distinct Secretase. / Alfalah, Marwan; Parkin, Edward T.; Jacob, Ralf et al.
In: Journal of Biological Chemistry, Vol. 276, No. 24, 15.06.2001, p. 21105-21109.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Alfalah, M, Parkin, ET, Jacob, R, Sturrock, ED, Mentele, R, Turner, AJ, Hooper, NM & Naim, HY 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, vol. 276, no. 24, pp. 21105-21109. https://doi.org/10.1074/jbc.M100339200

APA

Alfalah, M., Parkin, E. T., Jacob, R., Sturrock, E. D., Mentele, R., Turner, A. J., Hooper, N. M., & Naim, H. 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), 21105-21109. https://doi.org/10.1074/jbc.M100339200

Vancouver

Alfalah M, Parkin ET, Jacob R, Sturrock ED, Mentele R, Turner AJ et al. A Point Mutation in the Juxtamembrane Stalk of Human Angiotensin I-converting Enzyme Invokes the Action of a Distinct Secretase. Journal of Biological Chemistry. 2001 Jun 15;276(24):21105-21109. doi: 10.1074/jbc.M100339200

Author

Alfalah, Marwan ; Parkin, Edward T. ; Jacob, Ralf et al. / A Point Mutation in the Juxtamembrane Stalk of Human Angiotensin I-converting Enzyme Invokes the Action of a Distinct Secretase. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 24. pp. 21105-21109.

Bibtex

@article{90191e9cc5ee4c6aacc486dbf54e2d16,
title = "A Point Mutation in the Juxtamembrane Stalk of Human Angiotensin I-converting Enzyme Invokes the Action of a Distinct Secretase.",
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.",
author = "Marwan Alfalah and Parkin, {Edward T.} and Ralf Jacob and Sturrock, {Edward D.} and Reinhard Mentele and Turner, {Anthony J.} and Hooper, {Nigel M.} and Naim, {Hassan Y.}",
year = "2001",
month = jun,
day = "15",
doi = "10.1074/jbc.M100339200",
language = "English",
volume = "276",
pages = "21105--21109",
journal = "Journal of Biological Chemistry",
issn = "1083-351X",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "24",

}

RIS

TY - JOUR

T1 - A Point Mutation in the Juxtamembrane Stalk of Human Angiotensin I-converting Enzyme Invokes the Action of a Distinct Secretase.

AU - Alfalah, Marwan

AU - Parkin, Edward T.

AU - Jacob, Ralf

AU - Sturrock, Edward D.

AU - Mentele, Reinhard

AU - Turner, Anthony J.

AU - Hooper, Nigel M.

AU - Naim, Hassan Y.

PY - 2001/6/15

Y1 - 2001/6/15

N2 - 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.

AB - 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.

U2 - 10.1074/jbc.M100339200

DO - 10.1074/jbc.M100339200

M3 - Journal article

VL - 276

SP - 21105

EP - 21109

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 1083-351X

IS - 24

ER -