Estradiol activates the tyrosine kinase/p21 ras/MAP-kinase pathway in MCF-7 cells. The study shows that estradiol treatment of MCF-7 cells triggers rapid and transient activation of MAP kinases erk-1 and erk-2, increases the active form of p21 ras, and induces tyrosine phosphorylation of Shc and p190, as well as association of p190 with p21 ras-GAP. These effects are mediated by the estradiol receptor, which is required for MAP-kinase activation. The estradiol receptor activates c-src, which is an integral part of the signaling events mediated by the estradiol receptor. The study also shows that the estradiol receptor is responsible for the transduction pathway activation, as evidenced by the inhibition of estradiol's effects by the anti-estrogen ICI 182 780. The findings suggest that estradiol acts through the classical estradiol receptor to activate the tyrosine kinase/p21 ras/MAP-kinase pathway, which is involved in cell proliferation. The study also demonstrates that estradiol increases the amount of GTP-bound p21 ras and induces tyrosine phosphorylation of proteins associated with p21 ras-GAP. The results indicate that estradiol activates the pathway through the classical estradiol receptor, which is necessary for the activation of c-src and the subsequent signaling events. The study provides evidence that the estradiol receptor is a key mediator of the signaling pathway triggered by estradiol.Estradiol activates the tyrosine kinase/p21 ras/MAP-kinase pathway in MCF-7 cells. The study shows that estradiol treatment of MCF-7 cells triggers rapid and transient activation of MAP kinases erk-1 and erk-2, increases the active form of p21 ras, and induces tyrosine phosphorylation of Shc and p190, as well as association of p190 with p21 ras-GAP. These effects are mediated by the estradiol receptor, which is required for MAP-kinase activation. The estradiol receptor activates c-src, which is an integral part of the signaling events mediated by the estradiol receptor. The study also shows that the estradiol receptor is responsible for the transduction pathway activation, as evidenced by the inhibition of estradiol's effects by the anti-estrogen ICI 182 780. The findings suggest that estradiol acts through the classical estradiol receptor to activate the tyrosine kinase/p21 ras/MAP-kinase pathway, which is involved in cell proliferation. The study also demonstrates that estradiol increases the amount of GTP-bound p21 ras and induces tyrosine phosphorylation of proteins associated with p21 ras-GAP. The results indicate that estradiol activates the pathway through the classical estradiol receptor, which is necessary for the activation of c-src and the subsequent signaling events. The study provides evidence that the estradiol receptor is a key mediator of the signaling pathway triggered by estradiol.