Activation of protein kinase C or cAMP-dependent protein kinase increases phosphorylation of the c-erbA-encoded thyroid hormone receptor and of the v-erbA-encoded protein.

Goldberg, Yves; Glineur, Corine; Gesquière, Jean‐Claude; Ricouart, Annie; Sap, Jan; Vennström, Björn; Ghysdael, Jacques

doi:10.1002/j.1460-2075.1988.tb03088.x

Cited by 138 publications

(72 citation statements)

References 55 publications

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“…Several other nuclear proteins are also substrates for PKC in vitro [27-321. Histones H2B, H4 and Hl' [53,55], nuclear matrix proteins NP80 and NP33 [54], lamin B [56,57] as well as the nuclear proteins encoded by c-erbA [58] and ets-2 [59] are phosphorylated in response to TPA treatment in vivo. Thus, PKC could prove to be an essential kinase in the control of nuclear processes during, and in preparation for, cell growth and differentiation.…”

Section: Discussionmentioning

confidence: 99%

Protein kinase C phosphorylates DNA topoisomerase I

1989

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The induction of mammalian cell proliferation requires the expression of a specific set of genes. Tumor promoters stimulate cell growth by activating the Ca*+ and phospholipid-dependent protein kinase, protein kinase C (PKC). DNA topoisomerase I, a nuclear enzyme involved in transcription, was phosphorylated by activated PKC in vitro. Phosphorylation by PKC stimulated the DNA relaxation activity of topoisomerase I two-to threefold. Therefore, DNA topoisomerase I is a substrate for PKC-mediated activation by phosphorylation and may serve as a nuclear target of mitogenic signals generated by tumor promoters in vivo.

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Section: Discussionmentioning

confidence: 99%

Protein kinase C phosphorylates DNA topoisomerase I

1989

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“…The PKA phosphorylation sites in v-ERB A/T3R␣-1 are within a domain that we have previ-ously implicated as contributing to DNA sequence recognition by these receptors, suggesting that phosphorylation could potentially affect the DNA binding properties of these proteins (22,23,25,26,42). In this paper we show that phosphorylation of either v-ERB A or T3R␣-1 has little or no effect on the overall affinity of receptor for DNA.…”

mentioning

confidence: 54%

“…For example, both v-ERB A, and its progenitor, avian T3R␣-1, are phosphorylated by protein kinase A (PKA) in vitro and, apparently, in vivo (41,42). The major site of PKA phosphorylation in v-ERB A has been mapped to serine 16/serine 17 (Fig.…”

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confidence: 99%

“…The major site of PKA phosphorylation in v-ERB A has been mapped to serine 16/serine 17 (Fig. 1A); both amino acids represent consensus PKA sites, and prior studies did not determine which of the two, or if both, were phosphorylated (42). The same PKA site(s) also exist and are phosphorylated in the avian T3R␣-1 progenitor (denoted serine 28/serine 29 in the T3R-numbering system; Fig.…”

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confidence: 99%

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Phosphorylation of Thyroid Hormone Receptors by Protein Kinase A Regulates DNA Recognition by Specific Inhibition of Receptor Monomer Binding

Tzagarakis-Foster

Privalsky

1998

Journal of Biological Chemistry

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Thyroid hormone receptor (T3R) ␣-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 T3R␣-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 T3R␣ 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 T3R␣-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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“…Chicken TR␣1 (30,31) and rat TR␣2 (32) were also found to be phosphorylated. Therefore the different extents of phosphorylation at different sites in TR isoforms could affect their stability differently.…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific Stabilization of the Thyroid Hormone β1 Nuclear Receptor by Phosphorylation

Ting

Bhat

Wong

et al. 1997

Journal of Biological Chemistry

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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 ␤1 (TR␤1), but not subtype ␤2 or ␣1, was induced to express by okadaic acid (OA) in a concentrationdependent manner. The induced TR␤1 had immunoreactivity and partial V8 proteolytic maps similar to those of the transfected and in vitro translated human TR␤1 (h-TR␤1). The OA-induced expression of endogenous TR␤1 was, however, not observed in a variety of other cultured cell lines tested, indicating that the induction was cell type-dependent. TR␤1 induced by OA was a multisite phosphorylated protein, in which serine and threonine in a ratio of 10:1 were phosphorylated. The induced TR␤1 was functional as it could mediate the thyroid hormone-dependent transcriptional activity via several thyroid hormone response elements. The induction of endogenous TR␤1 expression by OA was not accompanied by an increase in mRNA levels but was the result of an increase in the stability of the TR␤1 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 TR␤1 could be conferred by phosphorylation.Thyroid hormone nuclear receptors (TRs) 1 are members of the steroid hormone/retinoic acid receptor superfamily. Two TR genes, TR␣ and TR␤, have been identified which are located on chromosome 17 and chromosome 3, respectively. Four isoforms, ␤1, ␤2, ␣1, and ␣2, are generated from each of two TR genes, ␣ and ␤, by alternative splicing (1, 2). They are transcription factors that regulate the expression of target genes by interacting with specific DNA sequences known as thyroid hormone response elements (TREs) in the promoter region of target genes (1, 2). The transcriptional activity of TRs is not only dependent on thyroid hormone 3,3Ј,5-triiodo-L-thyronine (T 3 ) but also on the type of TRE. Recent studies have indicated that the transcriptional activity of TRs is further modulated via interaction with four groups of cellular proteins: (a) members of the nuclear receptor superfamily, notably the retinoid X receptors (1, 2); (b) corepressors including p270/N-CoR (3), SMRT (4), TRUP (5), SHP (6), and TRACs (7); (c) coactivator SRC-1 (8); and (d) the tumor suppressor p53 (9). It is clear that regulation of the transcriptional activity of TRs is more complex than envisioned previously.One important but less well studied mode of modulation of TR activity is the regulation of TR expression at the protein level. TR␣1 and TR␤1 are differentially expressed at different developmental stages and at different levels in various tissues (10 -12). Moreover, using the specific T 3 binding activity and immunoreactivity as measures of the expressed receptor proteins, it was found that there are marked variations in the TR protein:mRNA ratios in different tissues (11, 12), suggesting isoform-and tissue-dependent posttra...

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Activation of protein kinase C or cAMP-dependent protein kinase increases phosphorylation of the c-erbA-encoded thyroid hormone receptor and of the v-erbA-encoded protein.

Cited by 138 publications

References 55 publications

Protein kinase C phosphorylates DNA topoisomerase I

Protein kinase C phosphorylates DNA topoisomerase I

Phosphorylation of Thyroid Hormone Receptors by Protein Kinase A Regulates DNA Recognition by Specific Inhibition of Receptor Monomer Binding

Tissue-specific Stabilization of the Thyroid Hormone β1 Nuclear Receptor by Phosphorylation

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