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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carcinoma, Squamous Cell
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Cathepsin B / antagonists & inhibitors
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Cathepsin B / metabolism
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Cathepsin H
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Cathepsin L
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Cathepsins / antagonists & inhibitors*
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Cathepsins / metabolism
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Cysteine Endopeptidases*
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Cysteine Proteinase Inhibitors*
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Electrophoresis, Polyacrylamide Gel
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Endopeptidases*
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ErbB Receptors / drug effects
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ErbB Receptors / metabolism*
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Genes, ras*
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Humans
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Immunoassay
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Papain / antagonists & inhibitors
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / pharmacology*
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Proto-Oncogene Proteins p21(ras)
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Skin Neoplasms
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Tumor Cells, Cultured
Substances
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Cysteine Proteinase Inhibitors
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Proto-Oncogene Proteins
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ErbB Receptors
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Cathepsins
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Endopeptidases
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Cysteine Endopeptidases
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Cathepsin B
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CTSL protein, human
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Cathepsin L
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CTSH protein, human
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Cathepsin H
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Papain
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HRAS protein, human
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Proto-Oncogene Proteins p21(ras)