scholarly journals A refractory phase in cyclic AMP-responsive transcription requires down regulation of protein kinase A.

1995 ◽  
Vol 15 (3) ◽  
pp. 1826-1832 ◽  
Author(s):  
R Armstrong ◽  
W Wen ◽  
J Meinkoth ◽  
S Taylor ◽  
M Montminy
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Protein Phosphatase ◽  
Refractory Period ◽  
Protein Phosphatase 1 ◽  
Creb Phosphorylation ◽  
Subunit Expression ◽  
C Subunit ◽  
Kinase A

Cyclic AMP (cAMP) stimulates the expression of numerous genes through the protein kinase A (PK-A)-mediated phosphorylation of the nuclear factor CREB at Ser-133 (G. A. Gonzalez and M. R. Montminy, Cell 59:675-680, 1989). Like other signal transduction pathways, cAMP induces gene expression with burst-attenuation kinetics; cAMP-dependent transcription and CREB phosphorylation peak within 30 min and decline steadily over the next 4 to 6 h via the protein phosphatase 1-mediated dephosphorylation of CREB (M. Hagiwara, A. Alberts, P. Brindle, J. Meinkoth, J. Feramisco, T. Deng, M. Karin, S. Shenolikar, and M. Montminy, Cell 70:105-113, 1992). Here we characterize a third phase in cAMP-responsive transcription--a refractory period during which hormone-treated cells become transcriptionally unresponsive to subsequent stimulation by cAMP. This refractory period begins 6 to 8 h after stimulation and lasts 3 to 5 days after the removal of hormone. In contrast to the earlier attenuation phase, transcription of cAMP-responsive genes during the refractory period is not restored by inhibitors of protein phosphatase 1 activity. Rather, the establishment and maintenance of this phase rely on a marked reduction in PK-A catalytic subunit expression at the translational level. As overexpression of C-subunit protein can reactive transcription of cAMP-responsive genes during the refractory period, our results suggest that hormone-responsive cells may stimulate, attenuate, and then silence signal-dependent genes through distinct regulatory mechanisms.

scholarly journals Coupling of hormonal stimulation and transcription via the cyclic AMP-responsive factor CREB is rate limited by nuclear entry of protein kinase A.

1993 ◽  
Vol 13 (8) ◽  
pp. 4852-4859 ◽  
Author(s):  
M Hagiwara ◽  
P Brindle ◽  
A Harootunian ◽  
R Armstrong ◽  
J Rivier ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Cellular Responses ◽  
Catalytic Subunit ◽  
Nuclear Entry ◽  
Creb Phosphorylation ◽  
Eukaryotic Genes ◽  
C Subunit ◽  
Kinase A

Cyclic AMP (cAMP) regulates a number of eukaryotic genes by mediating the protein kinase A (PKA)-dependent phosphorylation of the CREB transcription factor at Ser-133. In this study, we test the hypothesis that the stoichiometry and kinetics of CREB phosphorylation are determined by the liberation and subsequent translocation of PKA catalytic subunit (C subunit) into the nucleus. Using fluorescence imaging techniques, we observed that PKA was activated in a stimulus-dependent fashion that led to nuclear entry of C subunit over a 30-min period. The degree of CREB phosphorylation, assessed with antiserum specific for CREB phosphorylated at Ser-133, correlated with the amount of PKA liberated. The time course of phosphorylation closely paralleled the nuclear entry of the catalytic subunit. There was a linear relationship between the subsequent induction of the cAMP-responsive somatostatin gene and the degree of CREB phosphorylation, suggesting that each event--kinase activation, CREB phosphorylation, and transcriptional induction--was tightly coupled to the next. In contrast to other PKA-mediated cellular responses which are rapid and quantitative, the slow, incremental regulation of CREB activity by cAMP suggests that multifunctional kinases like PKA may coordinate cellular responses by dictating the kinetics and stoichiometry of phosphorylation for key substrates like CREB.

Coupling of hormonal stimulation and transcription via the cyclic AMP-responsive factor CREB is rate limited by nuclear entry of protein kinase A

1993 ◽  
Vol 13 (8) ◽  
pp. 4852-4859
Author(s):  
M Hagiwara ◽  
P Brindle ◽  
A Harootunian ◽  
R Armstrong ◽  
J Rivier ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Cellular Responses ◽  
Catalytic Subunit ◽  
Nuclear Entry ◽  
Creb Phosphorylation ◽  
Eukaryotic Genes ◽  
C Subunit ◽  
Kinase A

Cyclic AMP (cAMP) regulates a number of eukaryotic genes by mediating the protein kinase A (PKA)-dependent phosphorylation of the CREB transcription factor at Ser-133. In this study, we test the hypothesis that the stoichiometry and kinetics of CREB phosphorylation are determined by the liberation and subsequent translocation of PKA catalytic subunit (C subunit) into the nucleus. Using fluorescence imaging techniques, we observed that PKA was activated in a stimulus-dependent fashion that led to nuclear entry of C subunit over a 30-min period. The degree of CREB phosphorylation, assessed with antiserum specific for CREB phosphorylated at Ser-133, correlated with the amount of PKA liberated. The time course of phosphorylation closely paralleled the nuclear entry of the catalytic subunit. There was a linear relationship between the subsequent induction of the cAMP-responsive somatostatin gene and the degree of CREB phosphorylation, suggesting that each event--kinase activation, CREB phosphorylation, and transcriptional induction--was tightly coupled to the next. In contrast to other PKA-mediated cellular responses which are rapid and quantitative, the slow, incremental regulation of CREB activity by cAMP suggests that multifunctional kinases like PKA may coordinate cellular responses by dictating the kinetics and stoichiometry of phosphorylation for key substrates like CREB.

scholarly journals Full activation of a nuclear species of protein phosphatase-1 by phosphorylation with protein kinase A and casein kinase-2

1994 ◽  
Vol 297 (3) ◽  
pp. 447-449 ◽  
Author(s):  
A Van Eynde ◽  
M Beullens ◽  
W Stalmans ◽  
M Bollen
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Phosphatase ◽  
Fold Increase ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Catalytic Subunit ◽  
Protein Phosphatase 1 ◽  
Nuclear Species ◽  
Kinase A

Bovine thymus nuclei contain a species of protein phosphatase-1 (PP-1N alpha) that can be partially activated by phosphorylation of an associated inhibitory polypeptide, NIPP-1, with protein kinase A [Beullens, Van Eynde, Bollen and Stalmans (1993) J. Biol. Chem. 268, 13172-13177]. Here it is shown that PP-1N alpha can also be activated 4-fold by phosphorylation of NIPP-1 with casein kinase-2. The effects of protein kinase A and casein kinase-2 were additive, yielding an enzyme with an activity close to that of the free catalytic subunit. Casein kinase-2 introduced up to 1.2 phosphate groups into purified NIPP-1 on serine and threonine residues. This phosphorylation was associated with a 14-fold increase in the concentration of NIPP-1 required for 50% inhibition of the type-1 catalytic subunit. The kinase-mediated inactivation of NIPP-1 could be reversed by incubation with the catalytic subunit of protein phosphatase-2A.

scholarly journals Integrin Cross-talk in Endothelial Cells Is Regulated by Protein Kinase A and Protein Phosphatase 1

2008 ◽  
Vol 283 (46) ◽  
pp. 31849-31860 ◽  
Author(s):  
Annette M. Gonzalez ◽  
Jessica Claiborne ◽  
Jonathan C. R. Jones
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Cross Talk ◽  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Kinase A

Mn2+-dependent protein phosphatase 1 enhances protein kinase A-induced Ca2+ desensitisation in skinned murine myocardium

2007 ◽  
Vol 74 (1) ◽  
pp. 124-132 ◽  
Author(s):  
A NEULEN ◽  
N BLAUDECK ◽  
S ZITTRICH ◽  
D METZLER ◽  
G PFITZER ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Dependent Protein ◽  
Kinase A

scholarly journals Involvement of Salmonella Pathogenicity Island 2 in the Up-Regulation of Interleukin-10 Expression in Macrophages: Role of Protein Kinase A Signal Pathway

2004 ◽  
Vol 72 (4) ◽  
pp. 1964-1973 ◽  
Author(s):  
Kei-ichi Uchiya ◽  
Eduardo A. Groisman ◽  
Toshiaki Nikai
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinase A ◽  
Signal Transduction Pathway ◽  
Pathogenicity Island ◽  
Interleukin 10 ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Creb Phosphorylation ◽  
Kinase A

ABSTRACT Salmonellae are facultative intracellular bacteria capable of surviving within macrophages. Salmonella pathogenicity island 2 (SPI-2) is required for growth within macrophages and for virulence in mice. In this study, we show the involvement of SPI-2 in a signal transduction pathway that induces cytokine expression in Salmonella-infected macrophages. High levels of interleukin-10 (IL-10) mRNA were induced in macrophages by infection with wild-type salmonellae compared to a strain carrying a mutation in the spiC gene, which is encoded within SPI-2. The two strains had the same effect on the expression of proinflammatory cytokines such as IL-1α, IL-6, and tumor necrosis factor alpha. IL-10 expression was dose dependently blocked by treatment of infected macrophages with the protein kinase A (PKA) inhibitor H-89, while IL-10 expression was increased by the PKA activator dibutyryl cyclic AMP. Cyclic AMP-dependent PKA activity was higher in macrophages infected with wild-type salmonellae compared to the spiC mutant, and Ser132 phosphorylation of cyclic AMP response element-binding protein (CREB), which is an important mediator of PKA activation, correlated with the levels of PKA activity. Taken together, these results indicate that salmonellae cause an SPI-2-dependent increase in PKA activity that leads to CREB phosphorylation, resulting in up-regulation of IL-10 expression in Salmonella-infected macrophages. Suppression of IL-10 expression by an antisense oligonucleotide did not affect the growth of wild-type salmonellae within macrophages, whereas growth was dose dependently inhibited by H-89, suggesting that the PKA signaling pathway plays a significant role in intramacrophage Salmonella survival.

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