Heparan sulfate regulates ADAM12 through a molecular switch mechanism.

Research output: Contribution to journalJournal articlepeer-review

Standard

Heparan sulfate regulates ADAM12 through a molecular switch mechanism. / Sørensen, Hans P; Vives, Romain R; Manetopoulos, Christina; Albrechtsen, Reidar; Lydolph, Magnus C; Jacobsen, Jonas; Couchman, John R; Wewer, Ulla M.

In: Journal of Biological Chemistry, 2008.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Sørensen, HP, Vives, RR, Manetopoulos, C, Albrechtsen, R, Lydolph, MC, Jacobsen, J, Couchman, JR & Wewer, UM 2008, 'Heparan sulfate regulates ADAM12 through a molecular switch mechanism.', Journal of Biological Chemistry. https://doi.org/10.1074/jbc.M804113200

APA

Sørensen, H. P., Vives, R. R., Manetopoulos, C., Albrechtsen, R., Lydolph, M. C., Jacobsen, J., Couchman, J. R., & Wewer, U. M. (2008). Heparan sulfate regulates ADAM12 through a molecular switch mechanism. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.M804113200

Vancouver

Sørensen HP, Vives RR, Manetopoulos C, Albrechtsen R, Lydolph MC, Jacobsen J et al. Heparan sulfate regulates ADAM12 through a molecular switch mechanism. Journal of Biological Chemistry. 2008. https://doi.org/10.1074/jbc.M804113200

Author

Sørensen, Hans P ; Vives, Romain R ; Manetopoulos, Christina ; Albrechtsen, Reidar ; Lydolph, Magnus C ; Jacobsen, Jonas ; Couchman, John R ; Wewer, Ulla M. / Heparan sulfate regulates ADAM12 through a molecular switch mechanism. In: Journal of Biological Chemistry. 2008.

Bibtex

@article{58481780912511dd86a6000ea68e967b,
title = "Heparan sulfate regulates ADAM12 through a molecular switch mechanism.",
abstract = "The disintegrin and metalloproteases (ADAMs) are emerging as therapeutic targets in human disease, but specific drug design is hampered by potential redundancy. Unlike other metzincins, ADAM pro domains remain bound to the mature enzyme to regulate activity. Here ADAM12, a protease that promotes tumor progression and chondrocyte proliferation in osteoarthritic cartilage, is shown to possess a pro/catalytic domain cationic molecular switch, regulated by exogenous heparan sulfate and heparin but also endogenous cell surface proteoglycans and the polyanion, calcium pentosan polysulfate. Sheddase functions of ADAM12 are regulated by the switch, as are proteolytic functions in placental tissue and sera of pregnant women. Moreover, human heparanase, an enzyme also linked to tumorigenesis, can promote ADAM12 sheddase activity at the cell surface through cleavage of the inhibitory heparan sulfate. These data present a novel concept that might allow targeting of ADAM12 and suggest that other ADAMs may have specific regulatory activity embedded in their pro and catalytic domain structures.",
author = "S{\o}rensen, {Hans P} and Vives, {Romain R} and Christina Manetopoulos and Reidar Albrechtsen and Lydolph, {Magnus C} and Jonas Jacobsen and Couchman, {John R} and Wewer, {Ulla M}",
year = "2008",
doi = "10.1074/jbc.M804113200",
language = "English",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",

}

RIS

TY - JOUR

T1 - Heparan sulfate regulates ADAM12 through a molecular switch mechanism.

AU - Sørensen, Hans P

AU - Vives, Romain R

AU - Manetopoulos, Christina

AU - Albrechtsen, Reidar

AU - Lydolph, Magnus C

AU - Jacobsen, Jonas

AU - Couchman, John R

AU - Wewer, Ulla M

PY - 2008

Y1 - 2008

N2 - The disintegrin and metalloproteases (ADAMs) are emerging as therapeutic targets in human disease, but specific drug design is hampered by potential redundancy. Unlike other metzincins, ADAM pro domains remain bound to the mature enzyme to regulate activity. Here ADAM12, a protease that promotes tumor progression and chondrocyte proliferation in osteoarthritic cartilage, is shown to possess a pro/catalytic domain cationic molecular switch, regulated by exogenous heparan sulfate and heparin but also endogenous cell surface proteoglycans and the polyanion, calcium pentosan polysulfate. Sheddase functions of ADAM12 are regulated by the switch, as are proteolytic functions in placental tissue and sera of pregnant women. Moreover, human heparanase, an enzyme also linked to tumorigenesis, can promote ADAM12 sheddase activity at the cell surface through cleavage of the inhibitory heparan sulfate. These data present a novel concept that might allow targeting of ADAM12 and suggest that other ADAMs may have specific regulatory activity embedded in their pro and catalytic domain structures.

AB - The disintegrin and metalloproteases (ADAMs) are emerging as therapeutic targets in human disease, but specific drug design is hampered by potential redundancy. Unlike other metzincins, ADAM pro domains remain bound to the mature enzyme to regulate activity. Here ADAM12, a protease that promotes tumor progression and chondrocyte proliferation in osteoarthritic cartilage, is shown to possess a pro/catalytic domain cationic molecular switch, regulated by exogenous heparan sulfate and heparin but also endogenous cell surface proteoglycans and the polyanion, calcium pentosan polysulfate. Sheddase functions of ADAM12 are regulated by the switch, as are proteolytic functions in placental tissue and sera of pregnant women. Moreover, human heparanase, an enzyme also linked to tumorigenesis, can promote ADAM12 sheddase activity at the cell surface through cleavage of the inhibitory heparan sulfate. These data present a novel concept that might allow targeting of ADAM12 and suggest that other ADAMs may have specific regulatory activity embedded in their pro and catalytic domain structures.

U2 - 10.1074/jbc.M804113200

DO - 10.1074/jbc.M804113200

M3 - Journal article

C2 - 18801731

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

ER -

ID: 6399945