Mitogen-Activated Protein Kinase Regulates Nuclear Association of Human Progesterone Receptors

摘要: Breast cancers often have increased MAPK activity; this pathway may drive breast cancer cell growth by targeting steroid hormone receptors. phosphorylates human progesterone receptors (PRs) on Ser294, thus regulating several aspects of PR activity. To study the role Ser294 phosphorylation subcellular distribution, we stably expressed wild-type (wt) or S294A (Ser294 to Ala) PR-B in types. PRs phosphorylated were nuclear. Activation induced and rapid nuclear translocation wt, but not S294A, PR-B; both concentrated nucleus after progestin treatment. The kinase inhibitor, U0126, blocked epidermal factor progestin-induced wt PR, indicating a novel mechanism for localization. After treatment, underwent ligand-dependent down-regulation, while persisted nuclei. Prolonged treatment with U0126 export leptomycin B, promoted accumulation suggesting that degradation occurs cytoplasm requires MAPK-dependent export. Stabilization B also transcriptional activity, link between nucleocytoplasmic shuttling, receptor stability, function. These results support regulatory localization coupling multiple functions.