Cell surface colony-stimulating factor 1 can be cleaved by TNF-alpha converting enzyme or endocytosed in a clathrin-dependent manner.

Cell surface colony-stimulating factor 1 can be cleaved by TNF-alpha converting enzyme or endocytosed in a clathrin-dependent manner. Research Abstract Details 

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Cell surface colony-stimulating factor 1 can be cleaved by TNF-alpha converting enzyme or endocytosed in a clathrin-dependent manner. Abstract Text:

Keisuke Horiuchi,Takeshi Miyamoto,Hironari Takaishi,Akihiro Hakozaki,Naoto Kosaki,Yoshiteru Miyauchi,Mitsuru Furukawa,Jiro Takito,Hironori Kaneko,Kenichiro Matsuzaki,Hideo Morioka,Carl P Blobel,Yoshiaki Toyama,Keisuke Horiuchi,Takeshi Miyamoto,Hironari Takaishi,Akihiro Hakozaki,Naoto Kosaki,Yoshiteru Miyauchi,Mitsuru Furukawa,Jiro Takito,Hironori Kaneko,Kenichiro Matsuzaki,Hideo Morioka,Carl P Blobel,Yoshiaki Toyama,

CSF-1 is a hemopoietic growth factor, which plays an essential role in macrophage and osteoclast development. Alternative splice variants of CSF-1 are synthesized as soluble or membrane-anchored molecules, although membrane CSF-1 (mCSF-1) can be cleaved from the cell membrane to become soluble CSF-1. The activities involved in this proteolytic processing, also referred to as ectodomain shedding, remain poorly characterized. In the present study, we examined the properties of the mCSF-1 sheddase in cell-based assays. Shedding of mCSF-1 was up-regulated by phorbol ester treatment and was inhibited by the metalloprotease inhibitors GM6001 and tissue inhibitor of metalloproteases 3. Moreover, the stimulated shedding of mCSF-1 was abrogated in fibroblasts lacking the TNF-alpha converting enzyme (TACE, also known as a disintegrin and metalloprotease 17) and was rescued by expression of wild-type TACE in these cells, strongly suggesting that the stimulated shedding is TACE dependent. Additionally, we observed that mCSF-1 is predominantly localized to intracellular membrane compartments and is efficiently internalized in a clathrin-dependent manner. These results indicate that the local availability of mCSF-1 is actively regulated by ectodomain shedding and endocytosis. This mechanism may have important implications for the development and survival of monocyte lineage cells.

Cell surface colony-stimulating factor 1 can be cleaved by TNF-alpha converting enzyme or endocytosed in a clathrin-dependent manner. Publishing Authors By Initials

K Horiuchi,T Miyamoto,H Takaishi,A Hakozaki,N Kosaki,Y Miyauchi,M Furukawa,J Takito,H Kaneko,K Matsuzaki,H Morioka,CP Blobel,Y Toyama,K Horiuchi,T Miyamoto,H Takaishi,A Hakozaki,N Kosaki,Y Miyauchi,M Furukawa,J Takito,H Kaneko,K Matsuzaki,H Morioka,CP Blobel,Y Toyama,

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Cell surface colony-stimulating factor 1 can be cleaved by TNF-alpha converting enzyme or endocytosed in a clathrin-dependent manner. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 179

Page Numbers: 6715-24

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 15

MONTH: Nov

YEAR: 2007

Cell surface colony-stimulating factor 1 can be cleaved by TNF-alpha converting enzyme or endocytosed in a clathrin-dependent manner. Information

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LANGUAGE: eng

NlmUniqueID: 2985117

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AFFILIATION: Department of Anti-Aging Orthopedic Research, Keio University, School of Medicine, Tokyo, Japan. horiuchi@z3.keio.jp

Country: United States

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MEDLINETA: J Immunol

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