Stress-induced cytoplasmic localisation of the protein kinase A (PKA) regulatory subunit Bcy1 requires Sch9 and Yak1

2001 ◽  
Vol 1 (S1) ◽  
Author(s):  
G Griffioen ◽  
P Branduardi ◽  
B Ballarini ◽  
J Norbeck ◽  
B Baroni ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Regulatory Subunit ◽  
Pka Regulatory Subunit ◽  
Kinase A

scholarly journals PRKAR1A gene analysis and protein kinase A activity in endometrial tumors

2012 ◽  
Vol 19 (4) ◽  
pp. 457-462 ◽  
Author(s):  
A Tsigginou ◽  
E Bimpaki ◽  
M Nesterova ◽  
A Horvath ◽  
S Boikos ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Regulatory Subunit ◽  
Normal Endometrium ◽  
Protein Levels ◽  
Normal Tissues ◽  
Subunit Expression ◽  
Dependent Protein ◽  
Pka Regulatory Subunit ◽  
Kinase A

PRKAR1A codes for the type 1a regulatory subunit (RIα) of the cAMP-dependent protein kinase A (PKA), an enzyme with an important role in cell cycle regulation and proliferation. PKA dysregulation has been found in various tumors, and PRKAR1A-inactivating mutations have been reported in mostly endocrine neoplasias. In this study, we investigated PKA activity and the PRKAR1A gene in normal and tumor endometrium. Specimens were collected from 31 patients with endometrial cancer. We used as controls 41 samples of endometrium that were collected from surrounding normal tissues or from women undergoing gynecological operations for other reasons. In all samples, we sequenced the PRKAR1A-coding sequence and studied PKA subunit expression; we also determined PKA activity and cAMP binding. PRKAR1A mutations were not found. However, PKA regulatory subunit protein levels, both RIα and those of regulatory subunit type 2b (RIIβ), were lower in tumor samples; cAMP binding was also lower in tumors compared with normal endometrium (P<0.01). Free PKA activity was higher in tumor samples compared with that of control tissue (P<0.01). There are significant PKA enzymatic abnormalities in tumors of the endometrium compared with surrounding normal tissue; as these were not due to PRKAR1A mutations, other mechanisms affecting PKA function ought to be explored.

scholarly journals Anchoring of Protein Kinase A-Regulatory Subunit IIα to Subapically Positioned Centrosomes Mediates Apical Bile Canalicular Lumen Development in Response to Oncostatin M but Not cAMP

2007 ◽  
Vol 18 (7) ◽  
pp. 2745-2754 ◽  
Author(s):  
Kacper A. Wojtal ◽  
Dick Hoekstra ◽  
Sven C.D. van IJzendoorn
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Membrane Trafficking ◽  
Oncostatin M ◽  
Regulatory Subunit ◽  
Apical Surface ◽  
Dependent Manner ◽  
Anchoring Protein ◽  
Pka Regulatory Subunit ◽  
Kinase A

Oncostatin M and cAMP signaling stimulate apical surface-directed membrane trafficking and apical lumen development in hepatocytes, both in a protein kinase A (PKA)-dependent manner. Here, we show that oncostatin M, but not cAMP, promotes the A-kinase anchoring protein (AKAP)-dependent anchoring of the PKA regulatory subunit (R)IIα to subapical centrosomes and that this requires extracellular signal-regulated kinase 2 activation. Stable expression of the RII-displacing peptide AKAP-IS, but not a scrambled peptide, inhibits the association of RIIα with centrosomal AKAPs and results in the repositioning of the centrosome from a subapical to a perinuclear location. Concomitantly, common endosomes, but not apical recycling endosomes, are repositioned from a subapical to a perinuclear location, without significant effects on constitutive or oncostatin M-stimulated basolateral-to-apical transcytosis. Importantly, however, the expression of the AKAP-IS peptide completely blocks oncostatin M-, but not cAMP-stimulated apical lumen development. Together, the data suggest that centrosomal anchoring of RIIα and the interrelated subapical positioning of these centrosomes is required for oncostatin M-, but not cAMP-mediated, bile canalicular lumen development in a manner that is uncoupled from oncostatin M-stimulated apical lumen-directed membrane trafficking. The results also imply that multiple PKA-mediated signaling pathways control apical lumen development and that subapical centrosome positioning is important in some of these pathways.

scholarly journals Phosphorylation of protein kinase A (PKA) regulatory subunit RIα by protein kinase G (PKG) primes PKA for catalytic activity in cells

2018 ◽  
Vol 293 (12) ◽  
pp. 4411-4421 ◽  
Author(s):  
Kristofer J. Haushalter ◽  
Darren E. Casteel ◽  
Andrea Raffeiner ◽  
Eduard Stefan ◽  
Hemal H. Patel ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Kinase G ◽  
Regulatory Subunit ◽  
Pka Regulatory Subunit ◽  
Kinase A ◽  
In Cells

scholarly journals Inhibition of serine/threonine phosphatase enhances arachidonic acid-induced [Ca2+]i via protein kinase A

2009 ◽  
Vol 296 (1) ◽  
pp. C88-C96 ◽  
Author(s):  
Tomoyuki Saino ◽  
Eileen L. Watson
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Cell Types ◽  
Regulatory Subunit ◽  
Calyculin A ◽  
Anchoring Protein ◽  
Pka Regulatory Subunit ◽  
Pp2a Inhibitor ◽  
Kinase A

Arachidonic acid (AA) regulates intracellular calcium concentration ([Ca2+]i) in a variety of cell types including salivary cells. In the present study, the effects of serine/threonine phosphatases on AA-induced Ca2+ signaling in mouse parotid acini were determined. Mice were euthanized with CO2. Treatment of acini with the serine/threonine phosphatase inhibitor calyculin A blocked both thapsigargin- and carbachol-induced Ca2+ entry but resulted in an enhancement of AA-induced Ca2+ release and entry. Effects were mimicked by the protein phosphatase-1 (PP1) inhibitor tautomycin but were inhibited by the PP2A inhibitor okadaic acid. The protein kinase A (PKA) inhibitor PKI(14-22) significantly attenuated AA-induced enhancement of Ca2+ release and entry in the presence of calyculin A, whereas it had no effect on calyculin A-induced inhibition of thapsigargin-induced Ca2+ responses. The ryanodine receptor (RyR) inhibitor, tetracaine, and StHt-31, a peptide known to competitively inhibit type II PKA regulatory subunit binding to PKA-anchoring protein (AKAP), abolished calyculin A enhancement of AA-induced Ca2+ release and entry. StHt-31 also abolished forskolin potentiation of 4-chloro-3-ethylphenol (4-CEP) and AA on Ca2+ release but had no effect on 8-(4-methoxyphenylthio)-2′- O-methyladenosine-3′,5′-cAMP potentiation of 4-CEP responses. Results suggest that inhibition of PP1 results in an enhancement of AA-induced [Ca2+]i via PKA, AKAP, and RyRs.

scholarly journals Targeting the Regulatory Subunit R2Alpha of Protein Kinase A in Human Glioblastoma through shRNA-Expressing Lentiviral Vectors

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1361
Author(s):  
Maira Zorzan ◽  
Claudia Del Vecchio ◽  
Stefania Vogiatzis ◽  
Elisa Saccon ◽  
Cristina Parolin ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Lentiviral Vectors ◽  
Brain Parenchyma ◽  
Regulatory Subunit ◽  
Glioblastoma Cells ◽  
Cellular Models ◽  
Therapeutic Setting ◽  
Promising Target ◽  
Kinase A

Glioblastoma is the most malignant and most common form of brain tumor, still today associated with a poor 14-months median survival from diagnosis. Protein kinase A, particularly its regulatory subunit R2Alpha, presents a typical intracellular distribution in glioblastoma cells compared to the healthy brain parenchyma and this peculiarity might be exploited in a therapeutic setting. In the present study, a third-generation lentiviral system for delivery of shRNA targeting the regulatory subunit R2Alpha of protein kinase A was developed. Generated lentiviral vectors are able to induce an efficient and stable downregulation of R2Alpha in different cellular models, including non-stem and stem-like glioblastoma cells. In addition, our data suggest a potential correlation between silencing of the regulatory subunit of protein kinase A and reduced viability of tumor cells, apparently due to a reduction in replication rate. Thus, our findings support the role of protein kinase A as a promising target for novel anti-glioma therapies.

The crystal structure of yeast regulatory subunit reveals key evolutionary insights into Protein Kinase A oligomerization

2021 ◽  
pp. 107732
Author(s):  
Nicolás González Bardeci ◽  
Enzo Tofolón ◽  
Felipe Trajtenberg ◽  
Julio Caramelo ◽  
Nicole Larrieux ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Regulatory Subunit ◽  
Kinase A
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