title: Synthesis of human progesterone receptors in T47D cells. Nascent A- and B-receptors are active without a phosphorylation-dependent post-translational maturation step.
abstract: Human progesterone receptors (PR) are structurally complex. At basal states there are two forms: A-receptors of approximately 94 kDa and B-receptors which are triplets of approximately 114, 117, and 120 kDa. All the proteins bind hormone and are phosphorylated. By using PR-rich T47Dco human breast cancer cells, pulse-labeling with [35S]methionine, and receptor immunopurification with anti-PR monoclonal antibodies, we show that PR are synthesized as single B-proteins of 114 kDa and single A-proteins of 94 kDa. The mature B-triplets form 6-10 h later by post-translational phosphorylation at sites restricted to the B-proteins. This slow maturation is not required for PR activation to hormone binding states, however, since A- and B-receptors that are less than 15 min old respond to progestins by undergoing transformation and nuclear binding accompanied by a rapid secondary phosphorylation common to both proteins. These studies explain the complex structure of the mature human B-receptors and the transformed A- and B-receptors, and address issues dealing with A- and B-proreceptor synthesis and receptor activation rates.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
authors.forename: P L
authors.initials: PL
authors.lastname: Sheridan
authors.forename: M D
authors.initials: MD
authors.lastname: Francis
authors.forename: K B
authors.initials: KB
authors.lastname: Horwitz
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D010766:Phosphorylation; D011397:Promegestone / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011980:Receptors, Progesterone / Q000096:biosynthesis* / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D011498:Protein Precursors; D011980:Receptors, Progesterone; D011397:Promegestone