Cysteine proteinase-inhibitory activity of ras gene product is not affected by mutations at GTPase-activating protein-binding sites.
We have investigated the proteinase-inhibitory activity against cathepsin L of some c-Ha-ras gene products (p21s) with point mutations at position 12, 33 or 35, which affect the interaction with GTPase-activating protein (GAP). All of the full-length p21s examined showed similar inhibitory activities irrespective of the point mutation and the transforming activity. These results suggest that mutations at GAP-interacting sites have no effect on the proteinase-inhibitory activity of p21s and that the proteinase-inhibitory activity alone is not sufficient for the transformation caused by p21s.
Hiwasa
T
T
Division of Biochemistry, Chiba Cancer Center Research Institute, Japan.
Sawada
T
T
Sakiyama
S
S
Kominami
E
E
Katunuma
N
N
D000595:Amino Acid Sequence; D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors; D010450:Endopeptidases; D020690:GTPase-Activating Proteins; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics*; D016283:Proto-Oncogene Proteins p21(ras); D051381:Rats; D013552:Swine; D020703:ras GTPase-Activating Proteins
D015853:Cysteine Proteinase Inhibitors; D020690:GTPase-Activating Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D020703:ras GTPase-Activating Proteins; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534280:Ctsl protein, rat; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)