Conformational Differences Among Solution Structures of the Type Iα, IIα and IIβ Protein Kinase A Regulatory Subunit Homodimers: Role of the Linker Regions

2004 ◽  
Vol 337 (5) ◽  
pp. 1183-1194 ◽  
Author(s):  
Dominico Vigil ◽  
Donald K. Blumenthal ◽  
William T. Heller ◽  
Simon Brown ◽  
Jaume M. Canaves ◽  
...  
2018 ◽  
Vol 217 (6) ◽  
pp. 1895-1897 ◽  
Author(s):  
F. Donelson Smith ◽  
John D. Scott

The role of autophosphorylation of the type II regulatory subunit in activation of protein kinase A (PKA) has been a longstanding question. In this issue, Isensee et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201708053) use antibody tools that selectively recognize phosphorylated RII and the catalytic subunit active site to reexamine PKA holoenzyme activation mechanisms in neurons.


2005 ◽  
Vol 24 (5) ◽  
pp. 235-242 ◽  
Author(s):  
Chada S Reddy

Cyclic AMP is an important second messenger mediating the actions of many hormones and other ligands in a variety of cells. Cells of the developing organism are no exception. Once generated, it releases the catalytic subunit of protein kinase A (PKA) from the inhibitory influence of its regulatory subunit, which then migrates into the nucleus to phosphorylate and enhance the binding of relevant transcription factors to the promoter element CRE of genes involved in above cellular responses. This review summarizes the available data on the essential role of this pathway in embryonic development as well as the functionality, ontogeny and consequences of genetic and chemical disruption of this pathway in the developing orofacial structures, especially the secondary palate as influenced by the mycotoxin, secalonic acid D.


2014 ◽  
Vol 12 (02) ◽  
pp. 1441005 ◽  
Author(s):  
Olga N. Rogacheva ◽  
Vasiliy E. Stefanov ◽  
Boris F. Shchegolev ◽  
Elena A. Vershinina ◽  
Elena V. Savvateeva-Popova

Using the combination of molecular dynamics (MD) simulations and geometric clustering we analyzed the role of arginine at 209 position in the transition of protein kinase A Iα (PKA Iα) regulatory subunit A-domain from H- to B-conformation and stabilization of the latter. The mechanism underlying the role of the residue at position 209 in the realization of B-conformation includes: (1) possibility to bind the ligand tightly (if transition happens in the presence of cAMP), (2) capability to hold β2β3-loop in the correct conformation, (3) tendency of residue at 209 position to stabilize B-conformation in the absence and in presence of the ligand. In terms of the effect produced on transition of A-domain from H- to B-conformation in the presence of cAMP, mutational substitutions for R209 can be arranged in the following order: Glu(Gly)>Lys>Ile. In the absence of cAMP the order is different Lys>Gly>Glu>Ile. Thus, our results allow us to presume that the role of arginine at 209 position can be important though not crucial.


2005 ◽  
Vol 174 (11) ◽  
pp. 6847-6853 ◽  
Author(s):  
Robynn V. Schillace ◽  
Sarah F. Andrews ◽  
Sarah G. Galligan ◽  
Kimberly A. Burton ◽  
Holly J. Starks ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1361
Author(s):  
Maira Zorzan ◽  
Claudia Del Vecchio ◽  
Stefania Vogiatzis ◽  
Elisa Saccon ◽  
Cristina Parolin ◽  
...  

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.


2021 ◽  
pp. 107732
Author(s):  
Nicolás González Bardeci ◽  
Enzo Tofolón ◽  
Felipe Trajtenberg ◽  
Julio Caramelo ◽  
Nicole Larrieux ◽  
...  

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