Irreversible inhibition of v-src tyrosine kinase activity by herbimycin A and its abrogation by sulfhydryl compounds.
Herbimycin A, an antibiotic which reverses Rous sarcoma virus transformation, inhibited irreversibly the auto- and trans-phosphorylation activities of p60v-src in in vitro immune complex kinase assays. The addition of a sulfhydryl compound such as dithiothreitol, 2-mercaptoethanol, glutathione (reduced form) or cysteine abolished the ability of herbimycin A to inactivate p60v-src kinase as well as the ability to reverse transformed cell morphology, whereas the addition of oxidized glutathione, cystine or methionine showed no effect. The sulfhydryl alkylating reagent N-ethylmaleimide also, although less effectively, inactivated p60v-src kinase activity in vitro. These results suggest the likelihood that sulfhydryl groups of p60v-src are involved in the inactivation of v-src tyrosine kinase activity by herbimycin A.
Department of Antibiotics, National Institute of Health, Tokyo, Japan.
Y
Y
Uehara
H
H
Fukazawa
Y
Y
Murakami
S
S
Mizuno
D016227:Benzoquinones; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D047029:Lactams, Macrocyclic; D015394:Molecular Structure; D009857:Oncogenes; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D013438:Sulfhydryl Compounds; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases