Inhibition of protein kinase A phase delays the mammalian circadian clock

1999 ◽  
Vol 835 (2) ◽  
pp. 350-353 ◽  
Author(s):  
Jennifer M. Lee ◽  
Kathryn M. Schak ◽  
Mary E. Harrington
Keyword(s):  
Protein Kinase ◽  
Circadian Clock ◽  
Protein Kinase A ◽  
Kinase A

scholarly journals CNOT1 mediates phosphorylation via Protein kinase A on the circadian clock

2019 ◽  
Author(s):  
Yunfeng Zhang ◽  
Haitang Qin ◽  
Yongjie Feng ◽  
Peng Gao ◽  
Yingbin Zhong ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Circadian Clock ◽  
Protein Kinase A ◽  
Feedback Loop ◽  
Critical Role ◽  
Positive Element ◽  
Endogenous Protein ◽  
Genes Encoding ◽  
Genetic Deletion ◽  
Kinase A

AbstractAt the core of the mammalian circadian feedback loop, CLOCK (NPAS2)-BMAL1 is the positive element to activate transcription of downstream genes encoding the negative elements PERs and CRYs. Here we show that CNOT1 associates with both CLOCK and BMAL1, promotes their phosphorylation and increases their protein stability, and in turn inhibits the transcriptional activity of CLOCK-BMAL1. Expression of either CLOCK, BMAL1 or CNOT1 could interact with endogenous Protein Kinase A (PKA) as assessed by co-immunoprecipitation (Co-IP) and kinase assays. PKA could phosphorylate CLOCK and BMAL1 and this was promoted by CNOT1. Genetic deletion of PKA-Cα by CRISPR-Cas9 results in a longer period of the circadian rhythm; while overexpression of PKA-Cα induces a shorter period. Furthermore, we demonstrate that CNOT1 associates with CLOCK and BMAL1 in the mouse liver and promotes their phosphorylation. PER2, but not CRY2, is also a PKA target. Our results suggest that CNOT1 and PKA play a critical role in the mammalian circadian clock, revealing a conserved function in eukaryotic circadian regulations.

scholarly journals Role for Protein Kinase A in the Neurospora Circadian Clock by Regulating White Collar-IndependentfrequencyTranscription through Phosphorylation of RCM-1

2015 ◽  
Vol 35 (12) ◽  
pp. 2088-2102 ◽  
Author(s):  
Xiao Liu ◽  
Hongda Li ◽  
Qingqing Liu ◽  
Yanling Niu ◽  
Qiwen Hu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Circadian Clock ◽  
Protein Kinase A ◽  
White Collar ◽  
Content Type ◽  
Clock Gene Expression ◽  
Kinase A

Rhythmic activation and repression of clock gene expression is essential for the eukaryotic circadian clock functions. In theNeurosporacircadian oscillator, the transcription of thefrequency(frq) gene is periodically activated by the White Collar (WC) complex and suppressed by the FRQ-FRH complex. We previously showed that there is WC-independentfrqtranscription and its repression is required for circadian gene expression. How WC-independentfrqtranscription is regulated is not known. We show here that elevated protein kinase A (PKA) activity results in WC-independentfrqtranscription and the loss of clock function. We identified RCM-1 as the protein partner of RCO-1 and an essential component of the clock through its role in suppressing WC-independentfrqtranscription. RCM-1 is a phosphoprotein and is a substrate of PKAin vivoandin vitro. Mutation of the PKA-dependent phosphorylation sites on RCM-1 results in WC-independent transcription offrqand impaired clock function. Furthermore, we showed that RCM-1 is associated with the chromatin at thefrqlocus, a process that is inhibited by PKA. Together, our results demonstrate that PKA regulatesfrqtranscription by inhibiting RCM-1 activity through RCM-1 phosphorylation.

Serotonergic phase advances of the mammalian circadian clock involve protein kinase A and K+ channel opening

1994 ◽  
Vol 644 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Rebecca A. Prosser ◽  
H. Craig Heller ◽  
Joseph D. Miller
Keyword(s):  
Protein Kinase ◽  
Circadian Clock ◽  
Protein Kinase A ◽  
K Channel ◽  
Channel Opening ◽  
Kinase A

Regulation of spontaneous and induced resumption of meiosis in mouse oocytes by different intracellular pathways

Reproduction ◽  
2000 ◽  
pp. 377-383 ◽  
Author(s):  
L Leonardsen ◽  
A Wiersma ◽  
M Baltsen ◽  
AG Byskov ◽  
CY Andersen
Keyword(s):  
Signal Transduction ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Mitogen Activated Protein Kinase ◽  
Meiotic Maturation ◽  
Mouse Oocytes ◽  
Mitogen Activated Protein ◽  
Dependent Signal ◽  
Kinase Pathway ◽  
Kinase A

The mitogen-activated protein kinase-dependent and the cAMP-protein kinase A-dependent signal transduction pathways were studied in cultured mouse oocytes during induced and spontaneous meiotic maturation. The role of the mitogen-activated protein kinase pathway was assessed using PD98059, which specifically inhibits mitogen-activated protein kinase 1 and 2 (that is, MEK1 and MEK2), which activates mitogen-activated protein kinase. The cAMP-dependent protein kinase was studied by treating oocytes with the protein kinase A inhibitor rp-cAMP. Inhibition of the mitogen-activated protein kinase pathway by PD98059 (25 micromol l(-1)) selectively inhibited the stimulatory effect on meiotic maturation by FSH and meiosis-activating sterol (that is, 4,4-dimethyl-5alpha-cholest-8,14, 24-triene-3beta-ol) in the presence of 4 mmol hypoxanthine l(-1), whereas spontaneous maturation in the absence of hypoxanthine was unaffected. This finding indicates that different signal transduction mechanisms are involved in induced and spontaneous maturation. The protein kinase A inhibitor rp-cAMP induced meiotic maturation in the presence of 4 mmol hypoxanthine l(-1), an effect that was additive to the maturation-promoting effect of FSH and meiosis-activating sterol, indicating that induced maturation also uses the cAMP-protein kinase A-dependent signal transduction pathway. In conclusion, induced and spontaneous maturation of mouse oocytes appear to use different signal transduction pathways.

Regulation of Hepatic Glucose Production by Transforming Growth Factor Beta 1 via Protein Kinase A

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2441-PUB ◽  
Author(s):  
QUAN PAN ◽  
YUNMEI CHEN ◽  
HUI YAN ◽  
WANBAO YANG ◽  
ZHENG SHEN ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose ◽  
Growth Factor Beta ◽  
Kinase A
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