title: Inhibition of protein tyrosine kinase by 5-S-GAD, a novel antibacterial substance from an insect.
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.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo, 113, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hijikata
authors.forename: A
authors.initials: A
authors.lastname: Kobayashi
authors.forename: J Y
authors.initials: JY
authors.lastname: Leem
authors.forename: H
authors.initials: H
authors.lastname: Fukasawa
authors.forename: Y
authors.initials: Y
authors.lastname: Uehara
authors.forename: S
authors.initials: S
authors.lastname: Natori
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000890:Anti-Infective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002461:Cell Line, Transformed; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D004175:Diptera / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; C100496:N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine; D004295:Dihydroxyphenylalanine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005978:Glutathione