Inhibition of cathepsin L-induced degradation of epidermal growth factor receptors by c-Ha-ras gene products |
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Authors: | T Hiwasa S Sakiyama S Yokoyama J M Ha J Fujita S Noguchi Y Bando E Kominami N Katunuma |
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Affiliation: | Division of Biochemistry, Chiba Cancer Center Research Institute, Japan. |
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Abstract: | The inhibitory activities of c-Ha-ras gene products (p21s) toward several cysteine proteinases have been investigated. The activity of cathepsin L was inhibited by p21s most effectively while those of cathepsin B and papain were slightly inhibited by p21s. p21s did not show any inhibitory activity toward cathepsin H. In order to connect the protease-inhibitor activity of p21s with cell growth, the degradation of epidermal growth factor receptors (EGF-receptors) was investigated. EGF-receptors were preferentially cleaved by cathepsin L but not by cathepsin B or H. The cleavage of EGF-receptors by cathepsin L was inhibited by p21s dose-dependently. These results raise the possibility that p21s can suppress the degradation of growth-related proteins such as EGF-receptors and thereby affect cell growth. |
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