C-HA-RAS MUTANTS WITH POINT MUTATIONS IN GLN-VAL-VAL REGION HAVE REDUCED INHIBITORY ACTIVITY TOWARD CATHEPSIN-B

Protease-inhibitory activity of recombinant Ha-ras gene products (Ras) toward papain and cathepsins B and L was investigated. v-Ha-Ras showe d more potent inhibitory activity toward cathepsin B as compared with c-Ha-Ras. We have also investigated protease-inhibitory activity of c- Ha-Ras mutants with point mutations in amino acids between positions 2 3 and 50. Inhibitory activity of Ras toward papain and cathepsin L was not largely altered among mutants. However, the inhibitory activity t oward cathepsin B was significantly impaired by a mutation at position 43, 44, 45 or 48. These results suggest that 43Gln-Val-Val sequence p lays an important role at least to inhibit cathepsin B.