scholarly journals Nuclear Translocation of MEK1 Triggers a Complex T Cell Response through the Corepressor Silencing Mediator of Retinoid and Thyroid Hormone Receptor

2012 ◽  
Vol 190 (1) ◽  
pp. 159-167 ◽  
Author(s):  
Lei Guo ◽  
Chaoyu Chen ◽  
Qiaoling Liang ◽  
Mohammad Zunayet Karim ◽  
Magdalena M. Gorska ◽  
...  
Keyword(s):  
T Cell ◽  
Thyroid Hormone ◽  
Cell Response ◽  
Hormone Receptor ◽  
Nuclear Translocation ◽  
Thyroid Hormone Receptor ◽  
T Cell Response

Nuclear localization of protein kinase C-α induces thyroid hormone receptor-α1 expression in the cardiomyocyte

2006 ◽  
Vol 290 (1) ◽  
pp. H381-H389 ◽  
Author(s):  
Agnes Kenessey ◽  
Elizabeth Ann Sullivan ◽  
Kaie Ojamaa
Keyword(s):  
Protein Kinase C ◽  
Thyroid Hormone ◽  
Protein Kinase ◽  
Nuclear Localization ◽  
Hormone Receptor ◽  
Nuclear Translocation ◽  
Thyroid Hormone Receptor ◽  
Neonatal Rat ◽  
Cardiac Phenotype ◽  
Kinase C

Maladaptive cardiac hypertrophy results in phenotypic changes in several genes that are thyroid hormone responsive, suggesting that thyroid hormone receptor (TR) function may be altered by cellular kinases, including protein kinase C (PKC) isozymes that are activated in pathological hypertrophy. To investigate the role of PKC signaling in regulating TR function, cultured neonatal rat ventricular myocytes were transduced with adenovirus (Ad) expressing wild-type (wt) or kinase-inactive (dn) PKCα or constitutively active (ca) PKCδ and PKCε. Overexpression of wtPKCα, but not caPKCδ or caPKCε, induced a 28-fold increase ( P < 0.001) in TRα1 protein in the nuclear compartment and a smaller increase in the cytosol. Furthermore, TRα1 mRNA was increased 55-fold ( P < 0.001). This effect of PKCα was dependent on its kinase activity because dnPKCα was without effect. Phorbol 12-myristate 13-acetate (PMA) induced nuclear translocation of endogenous PKCα and Ad-wtPKCα concomitantly with an increase in nuclear TRα1 protein. In contrast, PMA-induced nuclear translocation of dnPKCα resulted in a decrease of TRα1. The increase in TRα1 protein in Ad-wtPKCα-transduced cardiomyocytes was not the result of a reduced rate of protein degradation, nor was the half-life of TRα1 mRNA prolonged, suggesting a PKCα-mediated effect on TRα transcription. Although phosphorylation of ERK1/2 was increased in Ad-wtPKCα-transduced cells, inhibition of phospho-ERK did not change TRα1 expression. PKCα overexpression in cardiomyocytes caused marked repression of triiodothyronine (T3)-responsive genes, α-myosin heavy chain, and the sarcoplasmic reticulum calcium-activated adenosinetriphosphatase SERCA2. Treatment with T3 for 4 h resulted in significant reductions of PKCα in nuclear and cytosolic compartments, and decreased TRα1 mRNA and protein, with normalization of phenotype. These results implicate PKCα as a regulator of TR function and suggest that nuclear localization of PKCα may control transcription of the TRα gene, and consequently, affect cardiac phenotype.

scholarly journals Thyroid hormone receptor TRβ1 mediates Akt activation by T3 in pancreatic β cells

2007 ◽  
Vol 38 (2) ◽  
pp. 221-233 ◽  
Author(s):  
Cecilia Verga Falzacappa ◽  
Eleonora Petrucci ◽  
Valentina Patriarca ◽  
Simona Michienzi ◽  
Antonio Stigliano ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Nuclear Translocation ◽  
Thyroid Hormone Receptor ◽  
Phosphatidylinositol 3 Kinase ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Akt Activation ◽  
Biological Responses ◽  
Confocal Immunofluorescence

It has recently been recognized that thyroid hormones may rapidly generate biological responses by non-genomic mechanisms that are unaffected by inhibitors of transcription and translation. The signal transduction pathways underlying these effects are just beginning to be defined. We demonstrated that thyroid hormone T3 rapidly induces Akt activation in pancreatic β cells rRINm5F and hCM via thyroid hormone receptor (TR) β1. The phosphorylation of Akt was T3 specific and dependent. Coimmunoprecipitation and colocalization experiments revealed that the phosphatidylinositol 3 kinase (PI3K) p85α subunit and the thyroid receptor β1 were able to form a complex at the cytoplasmic level in both the cell lines, suggesting that a ‘cytoplasmic TRβ1’ was implicated. Moreover, we evidenced that T3 treatment was able to induce kinase activity of the TRβ1-associated PI3K. The silencing of TRβ1 expression through RNAi confirmed this receptor to be crucial for the T3-induced activation of Akt. This action involved a T3-induced nuclear translocation of activated Akt, as demonstrated by confocal immunofluorescence. In summary, T3 is able to specifically activate Akt in the islet β cells rRINm5F and hCM through the interaction between TRβ1 and PI3K p85α, demonstrating the involvement of TRβ1 in this novel T3 non-genomic action in islet β cells.

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