Inhibition of protein tyrosine kinase by 5-S-GAD, a novel antibacterial substance from an insect

Biochem Biophys Res Commun. 1997 Aug 18;237(2):423-6. doi: 10.1006/bbrc.1997.7110.

Abstract

The effect of N-beta-alanyl-5-S-glutathionyl-dopa (5-S-GAD), a compound originally isolated from Sarcophaga peregrina (a flesh fly) as an antibacterial substance, on protein phosphorylation was examined using v-src-transformed NIH3T3 cell lysates. 5-S-GAD was found to inhibit tyrosine phosphorylation of protein tyrosine kinase v-src, but not serine/threonine phosphorylation of protein kinase C. The potency of this compound was comparable to that of herbimycin A. Our results suggested that a substitution at position 5 of the catechol in 5-S-GAD with the sulfur of cysteine is essential for 5-S-GAD to inhibit protein tyrosine kinase v-src.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Anti-Infective Agents / isolation & purification
  • Anti-Infective Agents / pharmacology*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Line, Transformed
  • Dihydroxyphenylalanine / analogs & derivatives*
  • Dihydroxyphenylalanine / isolation & purification
  • Dihydroxyphenylalanine / pharmacology
  • Diptera / chemistry*
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Glutathione / analogs & derivatives*
  • Glutathione / isolation & purification
  • Glutathione / pharmacology
  • Mice
  • Phosphorylation
  • Protein Kinase C / metabolism
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism

Substances

  • Anti-Infective Agents
  • Enzyme Inhibitors
  • N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine
  • Dihydroxyphenylalanine
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glutathione