cAMP oscillations restrict protein kinase A redistribution in insulin-secreting cells

2006 ◽  
Vol 34 (4) ◽  
pp. 498-501 ◽  
Author(s):  
O. Dyachok ◽  
J. Sågetorp ◽  
Y. Isakov ◽  
A. Tengholm
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Hormone Receptors ◽  
Nuclear Translocation ◽  
Epifluorescence Microscopy ◽  
Nuclear Entry ◽  
Spatial Redistribution ◽  
Insulin Secreting Cells ◽  
Time Courses ◽  
Kinase A

Activation of hormone receptors was recently found to evoke oscillations of the cAMP concentration ([cAMP]) beneath the plasma membrane of insulin-secreting cells. Here we investigate how different time courses of cAMP signals influence the generation of cytoplasmic Ca2+ signals and nuclear translocation of the PKA (protein kinase A) catalytic subunit in individual INS-1 β-cells. [cAMP] was measured with a fluorescent translocation biosensor and ratiometric evanescent wave microscopy. Analysis of PKA nuclear translocation was performed with epifluorescence microscopy and FlAsH (fluorescein arsenical helix binder) labelling of tetracysteine-tagged PKA-Cα subunit. Both oscillatory and stable elevations of [cAMP] induced by intermittent or constant inhibition of phosphodiesterases with isobutylmethylxanthine evoked Ca2+ spiking. During [cAMP] oscillations, the Ca2+ spiking was restricted to the periods of elevated [cAMP]. In contrast, only stable [cAMP] elevation induced nuclear entry of FlAsH-labelled PKA-Cα. These results indicate that oscillations of [cAMP] lead to selective target activation by restricting the spatial redistribution of PKA.

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.

Protein Kinase A phosphorylates NCoR to enhance its nuclear translocation and repressive function in human prostate cancer cells

2013 ◽  
Vol 228 (6) ◽  
pp. 1159-1165 ◽  
Author(s):  
Hyo-Kyoung Choi ◽  
Jung-Yoon Yoo ◽  
Mi-Hyeon Jeong ◽  
Soo-Yeon Park ◽  
Dong-Myoung Shin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Cancer Cells ◽  
Nuclear Translocation ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Kinase A

scholarly journals Phosphorylation of HSP90 by protein kinase A is essential for the nuclear translocation of androgen receptor

2019 ◽  
Vol 294 (22) ◽  
pp. 8699-8710 ◽  
Author(s):  
Manisha Dagar ◽  
Julie Pratibha Singh ◽  
Gunjan Dagar ◽  
Rakesh K. Tyagi ◽  
Gargi Bagchi
Keyword(s):  
Androgen Receptor ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Nuclear Translocation ◽  
Kinase A

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 Protein kinase A antagonist inhibits β-catenin nuclear translocation, c-Myc and COX-2 expression and tumor promotion in ApcMin/+ mice

2011 ◽  
Vol 10 (1) ◽  
pp. 149 ◽  
Author(s):  
Kristoffer W Brudvik ◽  
Jan E Paulsen ◽  
Einar M Aandahl ◽  
Borghild Roald ◽  
Kjetil Taskén
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Nuclear Translocation ◽  
Tumor Promotion ◽  
Cox 2 ◽  
Kinase A

scholarly journals Breaking Human Cytomegalovirus Major Immediate-Early Gene Silence by Vasoactive Intestinal Peptide Stimulation of the Protein Kinase A-CREB-TORC2 Signaling Cascade in Human Pluripotent Embryonal NTera2 Cells

2009 ◽  
Vol 83 (13) ◽  
pp. 6391-6403 ◽  
Author(s):  
Jinxiang Yuan ◽  
Xiaoqiu Liu ◽  
Allen W. Wu ◽  
Patrick W. McGonagill ◽  
Michael J. Keller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Vasoactive Intestinal Peptide ◽  
Human Cytomegalovirus ◽  
Immediate Early ◽  
Signaling Cascade ◽  
Nuclear Entry ◽  
Kinase A ◽  
Stimulation Of

ABSTRACT The triggering mechanisms underlying reactivation of human cytomegalovirus (HCMV) in latently infected persons are unclear. During latency, HCMV major immediate-early (MIE) gene expression breaks silence to initiate viral reactivation. Using quiescently HCMV-infected human pluripotent embryonal NTera2 cells (NT2) to model HCMV reactivation, we show that vasoactive intestinal peptide (VIP), an immunomodulatory neuropeptide, immediately and dose-dependently (1 to 500 nM) activates HCMV MIE gene expression. This response requires the MIE enhancer cyclic AMP response elements (CRE). VIP quickly elevates CREB Ser133 and ATF-1 Ser63 phosphorylation levels, although the CREB Ser133 phosphorylation level is substantial at baseline. VIP does not change the level of HCMV genomes in nuclei, Oct4 (pluripotent cell marker), or hDaxx (cellular repressor of HCMV gene expression). VIP-activated MIE gene expression is mediated by cellular protein kinase A (PKA), CREB, and TORC2. VIP induces PKA-dependent TORC2 Ser171 dephosphorylation and nuclear entry, which likely enables MIE gene activation, as TORC2 S171A (devoid of Ser171 phosphorylation) exhibits enhanced nuclear entry and desilences the MIE genes in the absence of VIP stimulation. In conclusion, VIP stimulation of the PKA-CREB-TORC2 signaling cascade activates HCMV CRE-dependent MIE gene expression in quiescently infected NT2 cells. We speculate that neurohormonal stimulation via this signaling cascade is a possible means for reversing HCMV silence in vivo.

scholarly journals Leydig Cells Express Follicle-Stimulating Hormone Receptors in African Catfish

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 357-365 ◽  
Author(s):  
Ángel García-López ◽  
Jan Bogerd ◽  
Joke C. M. Granneman ◽  
Wytske van Dijk ◽  
John M. Trant ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Leydig Cells ◽  
Hormone Receptors ◽  
Pubertal Development ◽  
Clarias Gariepinus ◽  
Receptor Expression ◽  
African Catfish ◽  
Testis Weight ◽  
Kinase A

This report aimed to establish, using African catfish, Clarias gariepinus, as model species, a basis for understanding a well-known, although not yet clarified, feature of male fish reproductive physiology: the strong steroidogenic activity of FSHs. Assays with gonadotropin receptor-expressing cell lines showed that FSH activated its cognate receptor (FSHR) with an at least 1000-fold lower EC50 than when challenging the LH receptor (LHR), whereas LH stimulated both receptors with similar EC50s. In androgen release bioassays, FSH elicited a significant response at lower concentrations than those required to cross-activate of the LHR, indicating that FSH stimulated steroid release via FSHR-dependent mechanisms. LHR/FSHR-mediated stimulation of androgen release was completely abolished by H-89, a specific protein kinase A inhibitor, pointing to the cAMP/protein kinase A pathway as the main route for both LH- and FSH-stimulated steroid release. Localization studies showed that intratubular Sertoli cells express FSHR mRNA, whereas, as reported for the first time in a vertebrate, catfish Leydig cells express both LHR and FSHR mRNA. Testicular FSHR and LHR mRNA expression increased gradually during pubertal development. FSHR, but not LHR, transcript levels continued to rise between completion of the first wave of spermatogenesis at about 7 months and full maturity at about 12 months of age, which was associated with a previously recorded approximately 3-fold increase in the steroid production capacity per unit testis weight. Taken together, our data strongly suggest that the steroidogenic potency of FSH can be explained by its direct trophic action on FSHR-expressing Leydig cells. In search of a mechanistic basis for the strong steroidogenic activity of fish FSH, we demonstrate FSH receptor expression by Leydig cells in catfish.

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