Phosphorylation stimulates the transcriptional activity of the human beta 1 thyroid hormone nuclear receptor.
- 15 August 1992
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 89 (16) , 7737-7741
- https://doi.org/10.1073/pnas.89.16.7737
Abstract
The role of phosphorylation on the gene activation activity of the human beta 1 thyroid hormone nuclear receptor (h-TR beta 1) was examined. h-TR beta 1 was found to be a phosphoprotein when expressed in COS-1 cells, with serine, threonine, and tyrosine (85:10:5) as the phosphorylation sites. Okadaic acid (a potent inhibitor of phosphatases 1 and 2A) at 0.1, 0.25, and 0.5 microM increased the phosphorylation of h-TR beta 1 by 3-, 7-, and 11-fold, respectively. The increase in phosphorylation was accompanied by a concomitant increase in phosphorylation was accompanied by a concomitant increase in receptor-mediated transcription in transient transfection assays. h-TR beta 1 purified from Escherichia coli was phosphorylated in vitro by the endogenous kinase from cellular extracts. Serine, threonine, and tyrosine were phosphorylated in a similar ratio to that found in COS-1 cells. The in vitro phosphorylation was stimulated by okadaic acid. Phosphorylation did not affect the binding of h-TR beta 1 to 3,3',5-triiodo-L-thyronine. However, phosphorylation of h-TR beta 1 resulted in an increase of its binding to DNA and conferred on it the ability to bind to nuclear accessory proteins. The results indicate that phosphorylation plays an important role in the transcriptional activity of h-TR beta 1.Keywords
This publication has 28 references indexed in Scilit:
- Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptorsCell, 1991
- The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptorsCell, 1991
- GC box binding induces phosphorylation of Sp1 by a DNA-dependent protein kinasePublished by Elsevier ,1990
- Commitment and activation at pol II promoters: A tail of protein-protein interactionsCell, 1990
- Activation in vitro of NF-κB" by phosphorylation of its inhibitor IκB"Nature, 1990
- Differential transcriptional activation by Oct-1 and Oct-2: Interdependent activation domains induce Oct-2 phosphorylationCell, 1990
- High level expression of p55, a thyroid hormone binding protein which is homologous to protein disulfide isomerase in a retroviral vectorBiochemical and Biophysical Research Communications, 1989
- DNA-binding activity of the adenovirus-induced E4F transcription factor is regulated by phosphorylation.Genes & Development, 1989
- Yeast heat shock factor is an essential DNA-binding protein that exhibits temperature-dependent phosphorylationCell, 1988
- Epidermal growth factor induces rapid tyrosine phosphorylation of proteins in A431 human tumor cellsCell, 1981