RECK forms cowbell-shaped dimers and inhibits matrix metalloproteinase-catalyzed cleavage of fibronectin.
The membrane-anchored protease regulator RECK plays important roles in mammalian development and tumor suppression. The biochemical bases of these bioactivities, however, remain poorly understood. Here we report on the properties of a recombinant RECK protein expressed in mouse fibroblasts and purified to near homogeneity. Multiple lines of evidence indicate that RECK forms dimers. Single particle reconstruction using transmission electron microscopy revealed a unique cowbell-like shaped RECK dimer. RECK is cleaved by MMP-2 and MMP-7 and competitively inhibits MMP-7-catalyzed cleavage of fibronectin. Forced RECK expression in HT1080 cells, whose endogenous RECK expression is minimal, leads to an increase in the amount of fibronectin associated with the cell. Our data demonstrate the ability of RECK to protect fibronectin from MMP-mediated degradation.
Omura
Akira
A
Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Matsuzaki
Tomoko
T
Mio
Kazuhiro
K
Ogura
Toshihiko
T
Yamamoto
Mako
M
Fujita
Akiko
A
Okawa
Katsuya
K
Kitayama
Hitoshi
H
Takahashi
Chiaki
C
Sato
Chikara
C
Noda
Makoto
M
D000818:Animals; D002460:Cell Line; D019281:Dimerization; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D058851:GPI-Linked Proteins; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020836:Protein Structure, Quaternary
D005353:Fibronectins; D058851:GPI-Linked Proteins; D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins; C115460:RECK protein, human; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2