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EMBO reports 6, 11, 1045–1051 (2005)
doi:10.1038/sj.embor.7400534
AOP Published online: 16 September 2005
Filamin is essential for shedding of the transmembrane serine protease, epithin
Chungho Kim1*, Yongcheol Cho1*, Chan-Hee Kang1, Moon Gyo Kim2†, HyoSeon Lee1, Eun-Gyung Cho1‡ & Dongeun Park1
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1 School of Biological Sciences, Seoul National University, Kwanak-gu, Shilim-dong, Seoul 151-742, Republic of Korea
2 Thymic Molecular Development Unit, Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
To whom correspondence should be addressed
Dongeun Park Tel: +82 2 880 5753; Fax: +82 2 872 1993; E-mail: depark@snu.ac.kr
† Present address: Department of Biological Sciences, Inha University, 253 Yonghyun-dong, Incheon 402-751, Republic of Korea
‡ Present address: Center for Neuroscience and Aging, The Burnham Institute, La Jolla, California 92037, USA
* These authors contributed equally to this work
Received 17 March 2005; Accepted 18 August 2005; Published online 16 September 2005.
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Abstract
Epithin is a type II transmembrane serine protease that exists in a soluble and membrane-bound form. Shedding is thought to be important in regulating its action, but little is known regarding the intracellular events that trigger such shedding. Here, we show that phorbol myristate acetate (PMA) causes the release of epithin. It also causes accumulation of the protein at the site of cell–cell contacts, and this accumulation is dependent on the formation of cortical actin. In addition, we have identified the actin-binding protein, filamin, as the linker between epithin and the actin cytoskeleton. The interaction of epithin and filamin was enhanced by PMA, and epithin was not released from filamin-deficient M2 cells. We also show that the release of epithin does not require its own activity and is blocked by a metalloprotease inhibitor, GM6001. These results show that filamin has an essential role in shedding by linking epithin to the as yet unidentified metalloprotease-shedding enzyme(s).
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