SERINE-167 IS THE MAJOR ESTRADIOL-INDUCED PHOSPHORYLATION SITE ON THEHUMAN ESTROGEN-RECEPTOR

Serine 167 has been identified by radiolabel and amino acid sequencing as the major estrogen-induced phosphorylation site on the human estro gen receptor (hER) from human MCF-7 mammary carcinoma cells. The phosp horylation of the hER on serine 167 was estrogen-dependent, increasing 4-fold upon estradiol treatment of MCF-7 cells and accounted for almo st half of the total [P-32]phosphate incorporated into the recombinant hER from Sf9 insect cells and the native hER from MCF-7 cells. Casein kinase II was found to phosphorylate the purified recombinant hER on serine 167 in vitro. In addition, estradiol binding enhanced by 2-fold the phosphorylation of the purified recombinant hER by casein kinase II in vitro. Western blot analysis and [P-32]phosphate incorporation c onfirmed the presence of casein kinase II in Sf9 cells. These results demonstrate that the hER is phosphorylated on serine 167 by casein kin ase II in a hormone-dependent manner.