The effect of quercetin on the phosphorylatio activity of the Rous sarcoma virus transforming gene product in vitro and in vivo

Abstract

The phosphotransferase activity of the Rous sarcoma virus src gene product, pp60^src, was inhibited both in vitro and in vivo by the bioflavonoid quercetin. The K_i for the inhibitory effect was in the range of 6–11μM under conditions in vitro. The inhibitory effect of quercetin was competitive towards the nucleotides ATP and GTP as substrates for pp60^src and was non‐competitive towards α‐casein as the protein substrate of this kinase activity. In contrast, studies in vitro of the phosphotransferase activity of the catalytic subunit of the cAMP‐dependent protein kinase showed that this flavonoid did not inhibit the phosphorylation of physiological substrates of this enzyme. In cultured cells the half‐maximal inhibition of tyrosine phosphorylation of pp60^src as well as the phosphorylation of the M_r= 34 000 protein, a physiological substrate of pp60^src, was in the range 0.06–0.08 mM.