Irreversible inhibition of v-src tyrosine kinase activity by herbimycin A and its abrogation by sulfhydryl compounds

Biochem Biophys Res Commun. 1989 Sep 15;163(2):803-9. doi: 10.1016/0006-291x(89)92293-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoquinones
  • Cell Survival / drug effects
  • Cells, Cultured
  • Electrophoresis, Polyacrylamide Gel
  • Lactams, Macrocyclic
  • Molecular Structure
  • Oncogenes*
  • Phosphorylation
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Quinones / pharmacology*
  • Rifabutin / analogs & derivatives
  • Sulfhydryl Compounds / pharmacology*

Substances

  • Benzoquinones
  • Lactams, Macrocyclic
  • Quinones
  • Sulfhydryl Compounds
  • Rifabutin
  • herbimycin
  • Protein-Tyrosine Kinases