scholarly journals Protein Kinase A Activation of Estrogen Receptor α Transcription Does Not Require Proteasome Activity and Protects the Receptor from Ligand-Mediated Degradation

Endocrinology ◽  
2004 ◽  
Vol 145 (6) ◽  
pp. 2730-2738 ◽  
Author(s):  
Houng-Wei Tsai ◽  
John A. Katzenellenbogen ◽  
Benita S. Katzenellenbogen ◽  
Margaret A. Shupnik
Keyword(s):  
Estrogen Receptor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Estrogen Receptor Α ◽  
Proteasome Activity ◽  
Kinase A

scholarly journals Phosphorylation of Human Estrogen Receptor α by Protein Kinase A Regulates Dimerization

1999 ◽  
Vol 19 (2) ◽  
pp. 1002-1015 ◽  
Author(s):  
Dongsheng Chen ◽  
Paul E. Pace ◽  
R. Charles Coombes ◽  
Simak Ali
Keyword(s):  
Estrogen Receptor ◽  
Protein Kinase ◽  
Dna Binding ◽  
Ligand Binding ◽  
Protein Kinase A ◽  
Estrogen Receptor Α ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Ici 182,780 ◽  
Kinase A

ABSTRACT Phosphorylation provides an important mechanism by which transcription factor activity is regulated. Estrogen receptor α (ERα) is phosphorylated on multiple sites, and stimulation of a number of growth factor receptors and/or protein kinases leads to ligand-independent and/or synergistic increase in transcriptional activation by ERα in the presence of estrogen. Here we show that ERα is phosphorylated by protein kinase A (PKA) on serine-236 within the DNA binding domain. Mutation of serine-236 to glutamic acid prevents DNA binding by inhibiting dimerization by ERα, whereas mutation to alanine has little effect on DNA binding or dimerization. Furthermore, PKA overexpression or activation of endogenous PKA inhibits dimerization in the absence of ligand. This inhibition is overcome by the addition of 17β-estradiol or the partial agonist 4-hydroxy tamoxifen. Interestingly, treatment with the complete antagonist ICI 182,780 does not overcome the inhibitory effect of PKA activation. Our results indicate that in the absence of ligand ERα forms dimers through interaction between DNA binding domains and that dimerization mediated by the ligand binding domain only occurs upon ligand binding but that the complete antagonist ICI 182,780 prevents dimerization through the ligand-binding domain. Heterodimer formation between ERα and ERβ is similarly affected by PKA phosphorylation of serine 236 of ERα. However, 4-hydroxytamoxifen is unable to overcome inhibition of dimerization by PKA. Thus, phosphorylation of ERα in the DNA binding domain provides a mechanism by which dimerization and thereby DNA binding by the estrogen receptor is regulated.

scholarly journals Effect of Follicle-Stimulating Hormone and Estrogen on the Expression of Betaglycan Messenger Ribonucleic Acid Levels in Cultured Rat Granulosa Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3379-3386 ◽  
Author(s):  
Yuki Omori ◽  
Kazuto Nakamura ◽  
Soichi Yamashita ◽  
Hiroko Matsuda ◽  
Tetsuya Mizutani ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Granulosa Cells ◽  
Luciferase Assay ◽  
Regulatory Function ◽  
Type Ii ◽  
Mrna Transcript ◽  
Inhibin A ◽  
Kinase A

Abstract Betaglycan (TGFβ type III receptor) was recently identified as a coreceptor to enhance the binding of inhibin A to activin type II receptor. This inhibin/betaglycan/activin type II receptor complex prevents activins from binding to their own receptors. The present study was undertaken to identify the expression and the regulation of the betaglycan gene in cultured rat granulosa cells. Northern blot analysis indicated betaglycan mRNA transcript of approximately 6.4 kbp. The treatment of the cells with FSH increased the betaglycan mRNA level, and a concurrent treatment with estradiol brought a significant increase in betaglycan mRNA. The protein kinase A activator, 8-bromoadenosine-cAMP, also increased the expression of its mRNA. Furthermore, betaglycan mRNA was induced additively by estradiol, which was blocked by estrogen receptor antagonists [ICI 182780, (R, R)-cis-diethyltetrahydro-2,8-chrysenediol]. In the luciferase assay, FSH altered the promoter activity of betaglycan. Moreover, when FSH plus estradiol was added to the granulosa cells, a significant increase in the half-life of betaglycan mRNA transcript was seen. In summary, FSH and estradiol increased betaglycan mRNA expression, most possibly through the protein kinase A pathway and the estrogen receptor-β. The increase of betaglycan mRNA was due to an increase in transcription and altered mRNA stability. In ovarian regulatory function, the expression of betaglycan may involve the functional antagonism of inhibin A in activin signal transduction.

scholarly journals Estradiol Modulates Translocator Protein (TSPO) and Steroid Acute Regulatory Protein (StAR) via Protein Kinase A (PKA) Signaling in Hypothalamic Astrocytes

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2976-2985 ◽  
Author(s):  
Claire Chen ◽  
John Kuo ◽  
Angela Wong ◽  
Paul Micevych
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Primary Cultures ◽  
Regulatory Protein ◽  
Estrogen Receptor Α ◽  
Translocator Protein ◽  
Calcium Stores ◽  
Female Rat ◽  
Transporter Protein ◽  
Kinase A

The ability of the central nervous system to synthesize steroid hormones has wide-ranging implications for physiology and pathology. Among the proposed roles of neurosteroids is the regulation of the LH surge. This involvement in the estrogen-positive feedback demonstrates the integration of peripheral steroids with neurosteroids. Within the female hypothalamus, estradiol from developing follicles stimulates progesterone synthesis in astrocytes, which activate neural circuits regulating gonadotropin (GnRH) neurons. Estradiol acts at membrane estrogen receptor-α to activate cellular signaling that results in the release of inositol trisphosphate-sensitive calcium stores that are sufficient to induce neuroprogesterone synthesis. The purpose of the present studies was to characterize the estradiol-induced signaling leading to activation of steroid acute regulatory protein (StAR) and transporter protein (TSPO), which mediate the rate-limiting step in steroidogenesis, ie, the transport of cholesterol into the mitochondrion. Treatment of primary cultures of adult female rat hypothalamic astrocytes with estradiol induced a cascade of phosphorylation that resulted in the activation of a calcium-dependent adenylyl cyclase, AC1, elevation of cAMP, and activation of both StAR and TSPO. Blocking protein kinase A activation with H-89 abrogated the estradiol-induced neuroprogesterone synthesis. Thus, together with previous results, these experiments completed the characterization of how estradiol action at the membrane leads to the augmentation of neuroprogesterone synthesis through increasing cAMP, activation of protein kinase A, and the phosphorylation of TSPO and StAR in hypothalamic astrocytes.

scholarly journals Growth Factor Regulation of Estrogen Receptor Coregulator PELP1 Functions via Protein Kinase A Pathway

2008 ◽  
Vol 6 (5) ◽  
pp. 851-861 ◽  
Author(s):  
Jatin K. Nagpal ◽  
Sujit Nair ◽  
Dimple Chakravarty ◽  
Rajib Rajhans ◽  
Saikumar Pothana ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Growth Factor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Kinase A ◽  
Growth Factor Regulation

Modulation of G Protein-Coupled Receptors by an Estrogen Receptor that Activates Protein Kinase A

1997 ◽  
Vol 51 (4) ◽  
pp. 605-612 ◽  
Author(s):  
Andre H. Lagrange ◽  
Oline K. Rønnekleiv ◽  
Martin J. Kelly
Keyword(s):  
Estrogen Receptor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled ◽  
Kinase A

scholarly journals 1′-Acetoxychavicol Acetate Increases Proteasome Activity by Activating cAMP-PKA Signaling

Planta Medica ◽  
2017 ◽  
Vol 84 (03) ◽  
pp. 153-159 ◽  
Author(s):  
Keisuke Yaku ◽  
Isao Matsui-Yuasa ◽  
Akiko Kojima-Yuasa
Keyword(s):  
Protein Kinase ◽  
Protein Degradation ◽  
Protein Kinase A ◽  
Pc12 Cells ◽  
Proteasome Activity ◽  
Dependent Protein Kinase ◽  
Differentiated Pc12 Cells ◽  
Age Related ◽  
Dependent Protein ◽  
Kinase A

AbstractProtein degradation systems are critical pathways for the maintenance of protein homeostasis. The age-dependent attenuation of the proteasome activity contributes to age-related neurodegenerative processes. The molecule 1′-acetoxychavicol acetate (ACA) is naturally obtained from the rhizomes and seeds of Zingiberaceae plants, such as Languas galangal and Alpinia galangal, and exhibits anti-carcinogenic effects. Recently, we have shown that ACA protected the age-related learning and memory impairments in senescence-accelerated mice and maintained cognitive performance. Therefore, we here examined the effects of ACA on the protein degradation systems and cell protection against neurotoxicity in differentiated PC12 cells. ACA increased proteasome activity in PC12 cells. Increased proteasome activity occurred during the initial stages of ACA treatment and lasted at least 9 h. The activity returned to control levels within 24 h. The increase in proteasome activity by ACA was suppressed by H-89, which is a cAMP-dependent protein kinase A inhibitor. ACA increased the adenylate cyclase activity and therefore the intracellular cAMP levels. Furthermore, ACA recovered the initial cell viability, which was reduced after the addition of the amyloid β-protein fragment to neuronally differentiated PC12 cells. The effects of ACA on amyloid toxicity were reduced after treatment with MG132, a proteasome inhibitor. These results demonstrated a neuroprotective effect of ACA via activation of cAMP/cAMP-dependent protein kinase A signaling in neuronally differentiated PC12 cells.

Sign in / Sign up

Export Citation Format

Share Document