Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy

Nature ◽  
10.1038/25367 ◽  
1998 ◽  
Vol 396 (6712) ◽  
pp. 687-690 ◽  
Author(s):  
Björn C. Schroeder ◽  
Christian Kubisch ◽  
Valentin Stein ◽  
Thomas J. Jentsch
Keyword(s):  
Cyclic Amp ◽  
Loss Of Function ◽  
K Channels

Regulation of maxi-K+ channels on pancreatic duct cells by cyclic AMP-dependent phosphorylation

1990 ◽  
Vol 115 (3) ◽  
pp. 203-215 ◽  
Author(s):  
M. A. Gray ◽  
J. R. Greenwell ◽  
A. J. Garton ◽  
B. E. Argent
Keyword(s):  
Cyclic Amp ◽  
Pancreatic Duct ◽  
K Channels ◽  
Duct Cells ◽  
Pancreatic Duct Cells

Role of Ca 2+ -Dependent K + Channels in Cerebral Vasodilatation Induced by Increases in Cyclic GMP and Cyclic AMP in the Rat

Stroke ◽  
1996 ◽  
Vol 27 (9) ◽  
pp. 1603-1608 ◽  
Author(s):  
Roberto Paternò ◽  
Frank M. Faraci ◽  
Donald D. Heistad
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
K Channels ◽  
Cerebral Vasodilatation

scholarly journals Transcriptional regulation of the mouse alpha A-crystallin gene: activation dependent on a cyclic AMP-responsive element (DE1/CRE) and a Pax-6-binding site.

1995 ◽  
Vol 15 (2) ◽  
pp. 653-660 ◽  
Author(s):  
A Cvekl ◽  
F Kashanchi ◽  
C M Sax ◽  
J N Brady ◽  
J Piatigorsky
Keyword(s):  
Cyclic Amp ◽  
Leukemia Virus ◽  
Consensus Sequence ◽  
Gene Activation ◽  
Type I ◽  
Loss Of Function ◽  
Mobility Shift ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
Responsive Element

Two cis-acting promoter elements (-108 to -100 and -49 to -33) of the mouse alpha A-crystallin gene, which is highly expressed in the ocular lens, were studied. Here we show that DE1 (-108 to -100; 5'TGACGGTG3'), which resembles the consensus cyclic AMP (cAMP)-responsive element sequence (CRE; 5'TGACGT[A/C][A/G]3'), behaves like a functional CRE site. Transfection experiments and electrophoretic mobility shift assays (EMSAs) using site-specific mutations correlated a loss of function with deviations from the CRE consensus sequence. Results of EMSAs in the presence of antisera against CREB, delta CREB, and CREM were consistent with the binding of CREB-like proteins to the DE1 sequence. Stimulation of alpha A-crystallin promoter activity via 8-bromo-cAMP, forskolin, or human T-cell leukemia virus type I Tax1 in transfections and reduction of activity of this site in cell-free transcription tests by competition with the somatostatin CRE supported the idea that DE1 is a functional CRE. Finally, Pax-6, a member of the paired-box family of transcription factors, activated the mouse alpha A-crystallin promoter in cotransfected COP-8 fibroblasts and bound to the -59 to -29 promoter sequence in EMSAs. These data provide evidence for a synergistic role of Pax-6 and CREB-like proteins for high expression of the mouse alpha A-crystallin gene in the lens.

scholarly journals The sak1+ gene of Schizosaccharomyces pombe encodes an RFX family DNA-binding protein that positively regulates cyclic AMP-dependent protein kinase-mediated exit from the mitotic cell cycle.

1995 ◽  
Vol 15 (3) ◽  
pp. 1479-1488 ◽  
Author(s):  
S Y Wu ◽  
M McLeod
Keyword(s):  
Protein Kinase ◽  
Dna Binding ◽  
Cyclic Amp ◽  
Stationary Phase ◽  
Schizosaccharomyces Pombe ◽  
Sexual Differentiation ◽  
Loss Of Function ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Diploid Cells

In Schizosaccharomyces pombe, meiosis is initiated by conditions of nutrient deprivation. Mutations in genes encoding elements of the cyclic AMP-dependent protein kinase (cAPK) pathway interfere with meiosis. Loss-of-function alleles of genes that stimulate the activity of cAPK allow cells to bypass the normal requirement of starvation for conjugation and meiosis. Alternatively, loss-of-function alleles of genes that inhibit cAPK lead to the inability to undergo sexual differentiation. The cgs1+ gene encodes the regulatory subunit of cAPK, and the cgs2+ gene encodes a cyclic AMP phosphodiesterase. Thus, both genes encode proteins which negatively regulate the activity of cAPK. Loss of either cgs1 or cgs2 prevents haploid cells from conjugating and diploid cells from undergoing meiosis. In addition to these defects, cells are unable to enter stationary phase. We describe a novel gene, sak1+, which when present on a plasmid overcomes the aberrant phenotypes associated with unregulated cAPK activity. Genetic analysis of sak1+ (suppressor of A-kinase) reveals that it functions downstream of cyclic AMP-dependent protein kinase to allow cells to exist the mitotic cycle and enter either stationary phase or the pathway leading to sexual differentiation. The sak1+ gene is essential for cell viability, and a null allele causes multiple defects in cell morphology and nuclear division. Thus, sak1+ is an important regulatory element in the life cycle of S. pombe. Sequence analysis shows that the predicted product of the sak1+ gene is an 87-kDa protein which shares homology to the RFX family of DNA-binding proteins identified in humans and mice. One member of this family, RFX1, is a transcription factor for a variety of viral and cellular genes.

scholarly journals Activation of the Pseudomonas aeruginosa AlgU Regulon through mucA Mutation Inhibits Cyclic AMP/Vfr Signaling

2010 ◽  
Vol 192 (21) ◽  
pp. 5709-5717 ◽  
Author(s):  
Adriana K. Jones ◽  
Nanette B. Fulcher ◽  
Grant J. Balzer ◽  
Mark L. Urbanowski ◽  
Christopher L. Pritchett ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cyclic Amp ◽  
Virulence Factors ◽  
Sigma Factor ◽  
Respiratory Infections ◽  
Response Regulator ◽  
Selective Advantage ◽  
Virulence Determinants ◽  
Loss Of Function ◽  
Chronic Infections

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that causes acute, invasive infections in immunocompromised individuals and chronic, persistent respiratory infections in individuals with cystic fibrosis (CF). The differential progression of acute or chronic infections involves the production of distinct sets of virulence factors. P. aeruginosa strains isolated from patients with acute respiratory infection are generally nonencapsulated and express a variety of invasive virulence factors, including flagella, the type III secretion system (T3SS), type IV pili (TFP), and multiple secreted toxins and degradative enzymes. Strains isolated from chronically infected CF patients, however, typically lack expression of invasive virulence factors and have a mucoid phenotype due to the production of an alginate capsule. The mucoid phenotype results from loss-of-function mutations in mucA, which encodes an anti-sigma factor that normally prevents alginate synthesis. Here, we report that the cyclic AMP/Vfr-dependent signaling (CVS) pathway is defective in mucA mutants and that the defect occurs at the level of vfr expression. The CVS pathway regulates the expression of multiple invasive virulence factors, including T3SS, exotoxin A, protease IV, and TFP. We further demonstrate that mucA-dependent CVS inhibition involves the alternative sigma factor AlgU (AlgT) and the response regulator AlgR but does not depend on alginate production. Our findings show that a single naturally occurring mutation leads to inverse regulation of virulence factors involved in acute and persistent infections. These results suggest that mucoid conversion and inhibition of invasive virulence determinants may both confer a selective advantage to mucA mutant strains of P. aeruginosa in the CF lung.

scholarly journals Steady-State Modulation of Voltage-Gated K+ Channels in Rat Arterial Smooth Muscle by Cyclic AMP-Dependent Protein Kinase and Protein Phosphatase 2B

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0121285 ◽  
Author(s):  
Jennifer L. Brignell ◽  
Matthew D. Perry ◽  
Carl P. Nelson ◽  
Jonathon M. Willets ◽  
R. A. John Challiss ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Steady State ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Phosphatase ◽  
Dependent Protein Kinase ◽  
K Channels ◽  
Voltage Gated ◽  
Protein Phosphatase 2B ◽  
Dependent Protein
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