The nonactivated estrogen receptor (naER) of the goat uterus is a tyrosine kinase.

The nonactivated estrogen receptor (naER) has been isolated and purified to absolute homogeneity from the goat uterine cytosol. It is a 66-kDa protein, sedimenting at 4.2 S on linear sucrose density gradients and having a Stokes radius of 36 A. It displays high affinity and specificity for estradiol and diethyl stilbestrol with a Kd of 1 x 10(-10) M. CNBr peptide analysis reveals that it has a primary structure distinctly different from that of the regular estrogen receptor even though anti-ER antibody cross-reacts with the nonactivated ER. The protein gains access to the DNA only upon dimerization with the estrogen receptor activation factor (E-RAF), a DNA-binding protein having no capacity to bind estradiol. Analysis reveals that both naER and E-RAF are protein kinases. While the E-RAF is a serine kinase, naER functions as a tyrosine kinase. No protein kinase activity is displayed by the regular estrogen receptor. The protein kinase activity of the naER is inhibited in the presence of estradiol. Similarly, the protein kinase activities associated with the proteins disappear when the naER and E-RAF are brought together.