Ectodomain shedding of nectin-1alpha by SF/HGF and TPA in MDCK cells.
Nectin is a Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecule implicated in the organization of the junctional complex comprised of E-cadherin-based adherens junctions and claudin-based tight junctions in epithelial cells. Scatter factor (SF)/hepatocyte growth factor (HGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor-promoting phorbol ester, induce cell spreading, followed by cell-cell dissociation and cell scattering, in Madin-Darby canine kidney (MDCK) cells. We found here that SF/HGF and TPA induced proteolytic cleavage of nectin-1alpha in the ectodomain, resulting in generation of the 80-kDa extracellular fragment and the 33-kDa fragment composed of the transmembrane and cytoplasmic domains, in MDCK cells. This shedding of nectin-1alpha was inhibited by metalloprotease inhibitors. These results indicate that SF/HGF and TPA induce the ectodomain shedding of nectin-1alpha presumably by a metalloprotease, and have raised the possibility that this shedding is involved in the SF/HGF- and TPA-induced cell-cell dissociation.
Tanaka
Yoshinari
Y
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Japan.
Irie
Kenji
K
Hirota
Takeshi
T
Sakisaka
Toshiaki
T
Nakanishi
Hiroyuki
H
Takai
Yoshimi
Y
D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000737:chemistry; D004285:Dogs; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D007136:Immunoglobulins / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D051379:Mice; D000075983:Nectins; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D007136:Immunoglobulins; D000075983:Nectins; D011993:Recombinant Fusion Proteins; D017228:Hepatocyte Growth Factor; D008666:Metalloendopeptidases; D013755:Tetradecanoylphorbol Acetate