scholarly journals Müllerian Inhibiting Substance Blocks the Protein Kinase A-Induced Expression of Cytochrome P450 17α-Hydroxylase/C17–20Lyase mRNA in a Mouse Leydig Cell Line Independent of cAMP Responsive Element Binding Protein Phosphorylation

Endocrinology ◽  
2002 ◽  
Vol 143 (9) ◽  
pp. 3351-3360 ◽  
Author(s):  
V. Matt Laurich ◽  
Alexander M. Trbovich ◽  
Francis H. O’Neill ◽  
Christopher P. Houk ◽  
Patrick M. Sluss ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Protein Kinase ◽  
Protein Phosphorylation ◽  
Protein Kinase A ◽  
Leydig Cell ◽  
Element Binding Protein ◽  
Responsive Element ◽  
Mouse Leydig Cell ◽  
Camp Responsive Element Binding ◽  
Kinase A

scholarly journals The role of protein kinase A pathway and cAMP responsive element-binding protein in androgen receptor-mediated transcription at the prostate-specific antigen locus

2005 ◽  
Vol 34 (1) ◽  
pp. 107-118 ◽  
Author(s):  
J Kim ◽  
L Jia ◽  
M R Stallcup ◽  
G A Coetzee
Keyword(s):  
Prostate Cancer ◽  
Signal Transduction ◽  
Androgen Receptor ◽  
Protein Kinase ◽  
Specific Antigen ◽  
Element Binding Protein ◽  
Responsive Element ◽  
Camp Responsive Element Binding ◽  
Kinase A ◽  
Androgen Independent

Androgen-independent prostate cancer is a lethal form of the disease that is marked by metastasis and rapid proliferation in its final stages. As no effective therapy for this aggressive tumor currently exists, it is imperative to elucidate and target the mechanisms involved in the progression to androgen independence. Accumulating evidence indicates that aberrant activation of androgen receptor (AR) via signal transduction pathways, AR gene mutation and/or amplification, and/or coregulator alterations may contribute to the progression of prostate cancer. In the present study, the effects of protein kinase A (PKA) signaling and its downstream factors on AR activity at the prostate-specific antigen (PSA) gene were tested. Activation of PKA by forskolin resulted in enhanced androgen-induced expression of the PSA gene, an effect that was blocked by the AR antagonist, bicalutamide. Interestingly, when either p300 or CBP was overexpressed, PKA activation was sufficient to stimulate PSA promoter-driven transcription in the absence of androgen, which was not inhibited by bicalutamide. PKA activation did not significantly alter AR protein levels but significantly increased the phosphorylated form of its downstream effector, cAMP responsive element-binding protein (CREB) in the presence of androgen. Furthermore, chromatin immunoprecipitation showed that the combination of androgen and forskolin increased phosphorylated CREB occupancy, which was accompanied by histone acetylation, at the putative cAMP responsive element located in the 5′ upstream regulatory region of the PSA gene. Remarkably, mammalian two-hybrid assay indicated that p300/CBP may bridge the interaction between AR and CREB, suggesting a novel enhanceosomal cooperation. These results demonstrate an intriguing interplay between a signal transduction pathway, coactivator overexpression and AR signaling as a possible combined mechanism of progression to androgen-independent prostate cancer.

In mpkCCD cells, long-term regulation of aquaporin-2 by vasopressin occurs independent of protein kinase A and CREB but may involve Epac

2012 ◽  
Vol 302 (11) ◽  
pp. F1395-F1401 ◽  
Author(s):  
Marleen L. A. Kortenoeven ◽  
Christiane Trimpert ◽  
Michiel van den Brand ◽  
Yuedan Li ◽  
Jack F. M. Wetzels ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Collecting Duct ◽  
Urine Concentration ◽  
Creb Phosphorylation ◽  
Aquaporin 2 ◽  
Element Binding Protein ◽  
Responsive Element ◽  
Kinase A

Urine concentration involves the hormone vasopressin (AVP), which stimulates cAMP production in renal principal cells, resulting in translocation and transcription of aquaporin-2 (AQP2) water channels, greatly increasing the water permeability, leading to a concentrated urine. As cAMP levels decrease shortly after AVP addition, whereas AQP2 levels still increase and are maintained for days, we investigated in the present study the mechanism responsible for the AQP2 increase after long-term 1-desamino-8-d-arginine vasopressin (dDAVP) application using mouse collecting duct (mpkCCD) cells. While 30 min of dDAVP incubation strongly increased cAMP, cAMP was lower with 1 day and was even further reduced with 4 days of dDAVP, although still significantly higher than in control cells. One day of dDAVP incubation increased AQP2 promoter-dependent transcription, which was blocked by the protein kinase A (PKA) inhibitor H89. Moreover, phosphorylation of the cAMP-responsive element binding protein (CREB) and CRE-dependent transcription was observed after short-term dDAVP stimulation. With 4 days of dDAVP, AQP2 transcription remained elevated, but this was not blocked by H89, and CRE-dependent transcription and CREB phosphorylation were not increased. Exchange factor directly activated by cAMP (Epac) 1 and 2 were found to be endogenously expressed in mpkCCD cells. Application of dDAVP increased the expression of Epac1, while Epac2 was reduced. Incubation with a specific Epac activator after dDAVP pretreatment increased both AQP2 abundance and transcription compared with cells left unstimulated the last day. In conclusion, the PKA-CRE pathway is involved in the initial rise in AQP2 levels after dDAVP stimulation but not in the long-term effect of dDAVP. Instead, long-term regulation of AQP2 may involve the activation of Epac.

scholarly journals cAMP/Protein Kinase A Signaling Inhibits Dlx5 Expression via Activation of CREB and Subsequent C/EBPβ Induction in 3T3-L1 Preadipocytes

2018 ◽  
Vol 19 (10) ◽  
pp. 3161 ◽  
Author(s):  
Hye-Lim Lee ◽  
Abdul Qadir ◽  
Hyun-Jung Park ◽  
Eunkyung Chung ◽  
Yun-Sil Lee ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Binding Protein ◽  
Negative Regulator ◽  
Transcriptional Suppression ◽  
Enhancer Binding Protein ◽  
Element Binding Protein ◽  
Responsive Element ◽  
The Impact ◽  
Kinase A

Distal-less homeobox 5 (Dlx5) is a negative regulator of adipogenesis. Dlx5 expression is decreased by adipogenic stimuli, but the mechanisms of Dlx5 downregulation by adipogenic stimuli have not yet been determined. Here, we tested the impact of cAMP/PKA (protein kinase A) signaling induced by 3-isobutyl-1 methyl xanthine (IBMX), forskolin, and 8-CPT-cAMP on the expression of Dlx5 in 3T3-L1 preadipocytes. Significant downregulation of Dlx5 mRNA expression and protein production levels were observed via cAMP/PKA-dependent signaling. Forced expression of cAMP-responsive element-binding protein (CREB) and CCAAT/enhancer-binding protein β (C/EBPβ) was sufficient for downregulation of Dlx5 expression and revealed that CREB functions upstream of C/EBPβ. In addition, C/EBPβ knockdown by siRNA rescued Dlx5 expression in IBMX-treated 3T3-L1 preadipocytes. Luciferase assays using a Dlx5-luc-2935 reporter construct demonstrated the requirement of the Dlx5 promoter region, ranging from −774 to −95 bp that contains two putative C/EBPβ binding elements (site-1: −517 to −510 bp and site-2: −164 to −157 bp), in the suppression of Dlx5 transcription. Consequently, chromatin immunoprecipitation analysis confirmed the importance of site-1, but not site-2, in C/EBPβ binding and transcriptional suppression of Dlx5. In conclusion, we elucidated the underling mechanism of Dlx5 downregulation in IBMX-induced adipogenesis. IBMX activated cAMP/PKA/CREB signaling and subsequently upregulated C/EBPβ, which binds to the Dlx5 promoter to suppress Dlx5 transcription.

scholarly journals Iron-responsive element-binding protein. Phosphorylation by protein kinase C.

1993 ◽  
Vol 268 (36) ◽  
pp. 27363-27370
Author(s):  
R S Eisenstein ◽  
P T Tuazon ◽  
K L Schalinske ◽  
S A Anderson ◽  
J A Traugh
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Phosphorylation ◽  
Binding Protein ◽  
Iron Responsive Element ◽  
Kinase C ◽  
Element Binding Protein ◽  
Responsive Element
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