v‐Ha‐Ras insertion/deletion mutants with reduced protease‐inhibitory activity have no transforming activity
- 8 March 1993
- journal article
- Published by Wiley in FEBS Letters
- Vol. 318 (3) , 297-300
- https://doi.org/10.1016/0014-5793(93)80532-y
Abstract
We have purified 26 insertion/deletion mutants of v-Ha-ras oncogene products produced by Escherichia coli and investigated their protease-inhibitory activity toward papain and cathepsins B and L. K i values for papain were relatively similar among the mutants, however, those for cathepsins B and L varied up to 10-fold. Among them, four mutants, 1–48 LIR 54–189, 1–110 LIS 112–189, 1–130 PDQ 146–189 and 1–155 LIR 166–189, showed significant reduction in the inhibitory activity toward cathepsin L and these four mutants have lost transforming activity toward NIH3T3 mouse fibroblasts. However, some other mutants also showed no transforming activity in spite of possession of the potent protease-inhibitory activity, suggesting that the protease-inhibitory activity of Ras might be necessary but not sufficient for its biological activity.Keywords
This publication has 20 references indexed in Scilit:
- The cystatins: Protein inhibitors of cysteine proteinasesPublished by Wiley ,2001
- Identification of amino acid residues of Ras protein that are essential for signal-transducing activity but not for enhancement of GTPase activity by GAPFEBS Letters, 1991
- Three-dimensional structures of H-ras p21 mutants: Molecular basis for their inability to function as signal switch moleculesCell, 1990
- Molecular Switch for Signal Transduction: Structural Differences Between Active and Inactive Forms of Protooncogenic ras ProteinsScience, 1990
- Cysteine proteinase inhibitors and rasgene products share the same biological activities including tranforming activity toward NIH3T3 mouse fibroblasts and the differentiation-inclucing activity toward PC12 rat pheochromocytoma cellsCarcinogenesis: Integrative Cancer Research, 1990
- All ras proteins are polyisoprenylated but only some are palmitoylatedCell, 1989
- Cysteine Proteinase-Inhibitory Activity ofrasGene Product is not Affected by Mutations at GTPase-Activating Protein-Binding SitesBiological Chemistry Hoppe-Seyler, 1989
- A Cytoplasmic Protein Stimulates Normal N- ras p21 GTPase, But Does Not Affect Oncogenic MutantsScience, 1987
- Degradation of a cAMP-binding protein is inhibited by human c-Ha-ras gene productsBiochemical and Biophysical Research Communications, 1987
- c‐Ha‐ras gene products are potent inhibitors of cathepsins B and LFEBS Letters, 1987