TY - JOUR
T1 - Phosphorylation of thyroid hormone receptors by protein kinase a regulates DNA recognition by specific inhibition of receptor monomer binding
AU - Tzagarakis-Foster, Christina
AU - Privalsky, Martin L.
PY - 1998/5/1
Y1 - 1998/5/1
N2 - Thyroid hormone receptor (T3R) α-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 T3Rα-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 T3Rα and by the v-ERB A onco-protein. 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 T3Rα-1 and v- ERB A by protein kinase A may provide a means of altering promoter recognition through a post-translational modification.
AB - Thyroid hormone receptor (T3R) α-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 T3Rα-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 T3Rα and by the v-ERB A onco-protein. 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 T3Rα-1 and v- ERB A by protein kinase A may provide a means of altering promoter recognition through a post-translational modification.
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U2 - 10.1074/jbc.273.18.10926
DO - 10.1074/jbc.273.18.10926
M3 - Article
C2 - 9556570
AN - SCOPUS:0032080118
VL - 273
SP - 10926
EP - 10932
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 18
ER -