Genistein, a specific inhibitor of tyrosine-specific protein kinases.

作者：Tetsu Akiyama, Junko Ishida, Shizue Nakagawa, Hiroshi Ogawara, Shun‐ichi Watanabe, Nobuko Itoh, Masabumi Shibuya, Yuko Fukami · 发表于：Journal of Biological Chemistry · 年份：1987 · DOI：10.1016/s0021-9258(18)45614-1 · 被引用次数：3750 · 研究领域：Phytoestrogen effects and research、Toxin Mechanisms and Immunotoxins、Diet, Metabolism, and Disease

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.