title: Compartment-specific phosphorylation of rat thyroid hormone receptor alpha1 regulates nuclear localization and retention.
abstract: The thyroid hormone receptor alpha1 (TRalpha1) is a transcription factor, which can activate or repress gene expression in response to thyroid hormone. In addition, some of its actions, including DNA binding and transcriptional activation, are thought to be regulated by phosphorylation. Results presented here, using Xenopus oocyte microinjection assays, demonstrate that a phosphorylated form of rat TRalpha1 is present in the nucleus, whereas unphosphorylated TRalpha1 remains cytoplasmic. Changes in the phosphorylation state of TRalpha1 occur rapidly and point to the possibility that phosphorylation occurs in the nucleus. Furthermore, increasing the overall phosphorylation state of the cell leads to enhanced nuclear retention of TRalpha1, suggesting that compartment-specific phosphorylation regulates nuclear localization of TRalpha1. Enhanced nuclear retention of TRalpha1 is not dependent on phosphorylation of serine 12, a well-characterized casein kinase II site, nor is phosphorylation of this site necessary for import of TRalpha1 into the Xenopus oocyte nucleus. Similarly, mutational analysis in mammalian cells shows that nuclear localization and partitioning of TRalpha1 to the nuclear matrix are independent of serine 12 phosphorylation. Taken together, these studies suggest that phosphorylation of one or more sites in TRalpha1, excluding serine 12, enhances nuclear retention and/or inhibits nuclear export but is not directly involved in nuclear import.
authors.affiliation: Department of Biology, College of William and Mary, PO Box 8795, Williamsburg, VA 23187, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Nicoll
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Gwinn
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Iwig
authors.forename: Preston P
authors.initials: PP
authors.lastname: Garcia
authors.forename: Caroline F
authors.initials: CF
authors.lastname: Bunn
authors.forename: Lizabeth A
authors.initials: LA
authors.lastname: Allison
mesh_terms: D000818:Animals; D001665:Binding Sites; D047390:Casein Kinase II; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D009865:Oocytes / Q000737:chemistry; D010766:Phosphorylation; D010957:Plasmids / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D051381:Rats; D037021:Thyroid Hormone Receptors alpha / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D008164:Luminescent Proteins; D037021:Thyroid Hormone Receptors alpha; D049452:Green Fluorescent Proteins; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases