Phosphorylation of thyroid hormone receptors by protein kinase A regulates DNA recognition by specific inhibition of receptor monomer binding.
Thyroid hormone receptor (T3R) alpha-1 and its oncogenic derivative, the v-ERB A protein, are phosphorylated by cAMP-dependent protein kinase A. Although this phosphorylation appears to be necessary for the oncogenic properties of v-ERB A, the mechanism by which phosphorylation influences the functions of v-ERB A and of the normal T3R has not been established. The protein kinase A phosphorylation site in T3Ralpha-1 is within a domain that is known to contribute to the DNA recognition properties of these receptors. We therefore analyzed the effects of protein kinase A phosphorylation on DNA recognition by the normal T3Ralpha and by the v-ERB A oncoprotein. We report here that phosphorylation of these receptor derivatives does not significantly alter the overall affinity of receptor dimers for DNA. However, phosphorylation does notably alter DNA recognition by preventing, or greatly inhibiting, the ability of these receptors to bind to DNA as protein monomers. These studies suggest that the phosphorylation of T3Ralpha-1 and v-ERB A by protein kinase A may provide a means of altering promoter recognition through a post-translational modification.
Tzagarakis-Foster
C
C
Section of Microbiology and Section of Molecular and Cellular Biology, Division of Biological Sciences, University of California, Davis, California 95616, USA.
Privalsky
M L
ML
D000595:Amino Acid Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D018774:Oncogene Proteins v-erbA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D018774:Oncogene Proteins v-erbA; D011988:Receptors, Thyroid Hormone; D004247:DNA; D017868:Cyclic AMP-Dependent Protein Kinases