Genistein, a specific inhibitor of tyrosine-specific protein kinases.
Tyrosine-specific protein kinase activity of the epidermal growth factor (EGF) receptor, pp60v-src and pp110gag-fes was inhibited in vitro by an isoflavone genistein. The inhibition was competitive with respect to ATP and noncompetitive to a phosphate acceptor, histone H2B. By contrast, genistein scarcely inhibited the enzyme activities of serine- and threonine-specific protein kinases such as cAMP-dependent protein kinase, phosphorylase kinase, and the Ca2+/phospholipid-dependent enzyme protein kinase C. When the effect of genistein on the phosphorylation of the EGF receptor was examined in cultured A431 cells, EGF-stimulated serine, threonine, and tyrosine phosphorylation was decreased. Phosphoamino acid analysis of total cell proteins revealed that genistein inhibited the EGF-stimulated increase in phosphotyrosine level in A431 cells.
D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D015683:Gene Products, gag; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D007700:Kinetics; D015688:Oncogene Protein pp60(v-src); D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012191:Retroviridae Proteins / Q000378:metabolism
D005419:Flavonoids; D015683:Gene Products, gag; D007529:Isoflavones; D012191:Retroviridae Proteins; D004815:Epidermal Growth Factor; D019833:Genistein; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src)