Inhibition of CREB Phosphorylation by Conjugates of Adenosine Analogues and Arginine-Rich Peptides, Inhibitors of PKA Catalytic Subunit

ChemBioChem ◽  
2014 ◽  
Vol 16 (2) ◽  
pp. 312-319 ◽  
Author(s):  
Marie Kriisa ◽  
Hedi Sinijärv ◽  
Angela Vaasa ◽  
Erki Enkvist ◽  
Sergiy Kostenko ◽  
...  
Keyword(s):  
Catalytic Subunit ◽  
Adenosine Analogues ◽  
Creb Phosphorylation ◽  
Pka Catalytic Subunit

scholarly journals Protein Kinase A Distribution in Meningioma

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1686 ◽  
Author(s):  
Caretta ◽  
Denaro ◽  
D’Avella ◽  
Mucignat-Caretta
Keyword(s):  
Brain Tissue ◽  
Catalytic Subunit ◽  
Therapeutic Interventions ◽  
Normal Brain ◽  
Local Concentration ◽  
Correlation Pattern ◽  
Catalytic Subunits ◽  
Tissue Specimens ◽  
Pka Catalytic Subunit

Deregulation of intracellular signal transduction pathways is a hallmark of cancer cells, clearly differentiating them from healthy cells. Differential intracellular distribution of the cAMP-dependent protein kinases (PKA) was previously detected in cell cultures and in vivo in glioblastoma and medulloblastoma. Our goal is to extend this observation to meningioma, to explore possible differences among tumors of different origins and prospective outcomes. The distribution of regulatory and catalytic subunits of PKA has been examined in tissue specimens obtained during surgery from meningioma patients. PKA RI subunit appeared more evenly distributed throughout the cytoplasm, but it was clearly detectable only in some tumors. RII was present in discrete spots, presumably at high local concentration; these aggregates could also be visualized under equilibrium binding conditions with fluorescent 8-substituted cAMP analogues, at variance with normal brain tissue and other brain tumors. The PKA catalytic subunit showed exactly overlapping pattern to RII and in fixed sections could be visualized by fluorescent cAMP analogues. Gene expression analysis showed that the PKA catalytic subunit revealed a significant correlation pattern with genes involved in meningioma. Hence, meningioma patients show a distinctive distribution pattern of PKA regulatory and catalytic subunits, different from glioblastoma, medulloblastoma, and healthy brain tissue. These observations raise the possibility of exploiting the PKA intracellular pathway as a diagnostic tool and possible therapeutic interventions.

scholarly journals Activity, expression and function of a second Drosophila protein kinase A catalytic subunit gene.

Genetics ◽  
1995 ◽  
Vol 141 (4) ◽  
pp. 1507-1520 ◽  
Author(s):  
A Meléndez ◽  
W Li ◽  
D Kalderon
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Essential Gene ◽  
Sequence Similarity ◽  
Catalytic Subunit ◽  
Subunit Gene ◽  
Drosophila Protein ◽  
Pka Catalytic Subunit ◽  
Kinase A

Abstract The DC2 gene was isolated previously on the basis of sequence similarity to DC0, the major Drosophila protein kinase A (PKA) catalytic subunit gene. We show here that the 67-kD Drosophila DC2 protein behaves as a PKA catalytic subunit in vitro. DC2 is transcribed in mesodermal anlagen of early embryos. This expression depends on dorsal but on neither twist nor snail activity. DC2 transcriptional fusions mimic this embryonic expression and are also expressed in subsets of cells in the optic lamina, wing disc and leg discs of third instar larvae. A saturation screen of a small deficiency interval containing DC2 for recessive lethal mutations yielded no DC2 alleles. We therefore isolated new deficiencies to generate deficiency trans-heterozygotes that lacked DC2 activity. These animals were viable and fertile. The absence of DC2 did not affect the viability or phenotype of imaginal disc cells lacking DC0 activity or embryonic hatching of animals with reduced DC0 activity. Furthermore, transgenes expressing DC2 from a DC0 promoter did not efficiently rescue a variety of DC0 mutant phenotypes. These observations indicate that DC2 is not an essential gene and is unlikely to be functionally redundant with DC0, which has multiple unique functions during development.

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.

Stimulation of c-Rel transcriptional activity by PKA catalytic subunit ?

2004 ◽  
Vol 82 (9) ◽  
Author(s):  
Shih-Hung Yu ◽  
Wei-Chung Chiang ◽  
Hsiu-Ming Shih ◽  
Kou-Juey Wu
Keyword(s):  
Transcriptional Activity ◽  
Catalytic Subunit ◽  
Pka Catalytic Subunit ◽  
Stimulation Of

scholarly journals PKA catalytic subunit compartmentation regulates contractile and hypertrophic responses to β-adrenergic signaling

2014 ◽  
Vol 66 ◽  
pp. 83-93 ◽  
Author(s):  
Jason H. Yang ◽  
Renata K. Polanowska-Grabowska ◽  
Jeffrey S. Smith ◽  
Charles W. Shields ◽  
Jeffrey J. Saucerman
Keyword(s):  
Catalytic Subunit ◽  
Adrenergic Signaling ◽  
Pka Catalytic Subunit

TSH Control of PKA Catalytic Subunit Activity in Thyroid Cell Cultures

1999 ◽  
Vol 266 (1) ◽  
pp. 15-18 ◽  
Author(s):  
M. Ben Abdelkhalek ◽  
A. Mamoune ◽  
P. Crisanti ◽  
B. Omri ◽  
B. Haye ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Catalytic Subunit ◽  
Thyroid Cell ◽  
Pka Catalytic Subunit

scholarly journals PKA catalytic subunit mutations in adrenocortical Cushing’s adenoma impair association with the regulatory subunit

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Davide Calebiro ◽  
Annette Hannawacker ◽  
Sandra Lyga ◽  
Kerstin Bathon ◽  
Ulrike Zabel ◽  
...  
Keyword(s):  
Catalytic Subunit ◽  
Regulatory Subunit ◽  
Pka Catalytic Subunit
Sign in / Sign up

Export Citation Format

Share Document