Tissue-specific stabilization of the thyroid hormone beta1 nuclear receptor by phosphorylation.
The present study evaluated the expression and regulation of endogenous thyroid hormone receptors (TRs) in cultured cells. In COS-1 cells, the endogenous TR, subtype beta1 (TRbeta1), but not subtype beta2 or alpha1, was induced to express by okadaic acid (OA) in a concentration-dependent manner. The induced TRbeta1 had immunoreactivity and partial V8 proteolytic maps similar to those of the transfected and in vitro translated human TRbeta1 (h-TRbeta1). The OA-induced expression of endogenous TRbeta1 was, however, not observed in a variety of other cultured cell lines tested, indicating that the induction was cell type-dependent. TRbeta1 induced by OA was a multisite phosphorylated protein, in which serine and threonine in a ratio of 10:1 were phosphorylated. The induced TRbeta1 was functional as it could mediate the thyroid hormone-dependent transcriptional activity via several thyroid hormone response elements. The induction of endogenous TRbeta1 expression by OA was not accompanied by an increase in mRNA levels but was the result of an increase in the stability of the TRbeta1 protein. This is the first report to indicate that one of the mechanisms by which the TR isoforms are differentially expressed is via the tissue-specific stabilization of the TR isoform proteins. Furthermore, this selective stability of TRbeta1 could be conferred by phosphorylation.
Ting
Y T
YT
Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892-4255, USA.
Bhat
M K
MK
Wong
R
R
Cheng
S y
Sy
D000818:Animals; D019556:COS Cells; D002460:Cell Line; D006801:Humans; D019319:Okadaic Acid / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D010750:Phosphoproteins; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D019319:Okadaic Acid