scholarly journals Protein kinase A activation: Something new under the sun?

2018 ◽  
Vol 217 (6) ◽  
pp. 1895-1897 ◽  
Author(s):  
F. Donelson Smith ◽  
John D. Scott
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Active Site ◽  
Catalytic Subunit ◽  
Regulatory Subunit ◽  
The Sun ◽  
Type Ii ◽  
Activation Mechanisms ◽  
Kinase A

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.

scholarly journals Candida albicans Lacking the Gene Encoding the Regulatory Subunit of Protein Kinase A Displays a Defect in Hyphal Formation and an Altered Localization of the Catalytic Subunit

2004 ◽  
Vol 3 (1) ◽  
pp. 190-199 ◽  
Author(s):  
Alejandro Cassola ◽  
Marc Parrot ◽  
Susana Silberstein ◽  
Beatrice B. Magee ◽  
Susana Passeron ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Protein Kinase ◽  
Fusion Protein ◽  
Protein Kinase A ◽  
Double Mutant ◽  
Catalytic Subunit ◽  
Regulatory Subunit ◽  
Wild Type ◽  
Gfp Fusion Protein ◽  
Kinase A

ABSTRACT The fungal pathogen Candida albicans switches from a yeast-like to a filamentous mode of growth in response to a variety of environmental conditions. We examined the morphogenetic behavior of C. albicans yeast cells lacking the BCY1 gene, which encodes the regulatory subunit of protein kinase A. We cloned the BCY1 gene and generated a bcy1 tpk2 double mutant strain because a homozygous bcy1 mutant in a wild-type genetic background could not be obtained. In the bcy1 tpk2 mutant, protein kinase A activity (due to the presence of the TPK1 gene) was cyclic AMP independent, indicating that the cells harbored an unregulated phosphotransferase activity. This mutant has constitutive protein kinase A activity and displayed a defective germinative phenotype in N-acetylglucosamine and in serum-containing medium. The subcellular localization of a Tpk1-green fluorescent protein (GFP) fusion protein was examined in wild-type, tpk2 null, and bcy1 tpk2 double mutant strains. The fusion protein was observed to be predominantly nuclear in wild-type and tpk2 strains. This was not the case in the bcy1 tpk2 double mutant, where it appeared dispersed throughout the cell. Coimmunoprecipitation of Bcy1p with the Tpk1-GFP fusion protein demonstrated the interaction of these proteins inside the cell. These results suggest that one of the roles of Bcy1p is to tether the protein kinase A catalytic subunit to the nucleus.

A novel activating effect of the regulatory subunit of protein kinase A on catalytic subunit activity

2008 ◽  
Vol 480 (2) ◽  
pp. 95-103 ◽  
Author(s):  
Jimena Rinaldi ◽  
Josefina Ocampo ◽  
Silvia Rossi ◽  
Silvia Moreno
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Catalytic Subunit ◽  
Regulatory Subunit ◽  
Kinase A

scholarly journals Protein kinase A type II-α regulatory subunit regulates the response of prostate cancer cells to taxane treatment

Cell Cycle ◽  
2014 ◽  
Vol 13 (20) ◽  
pp. 3292-3301 ◽  
Author(s):  
Evan R Zynda ◽  
Vitaliy Matveev ◽  
Michael Makhanov ◽  
Alexander Chenchik ◽  
Eugene S Kandel
Keyword(s):  
Prostate Cancer ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Cancer Cells ◽  
Regulatory Subunit ◽  
Type Ii ◽  
Prostate Cancer Cells ◽  
Kinase A

scholarly journals Unidirectional allostery in the regulatory subunit RIα facilitates efficient deactivation of protein kinase A

2016 ◽  
Vol 113 (44) ◽  
pp. E6776-E6785 ◽  
Author(s):  
Cong Guo ◽  
Huan-Xiang Zhou
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Structural Similarity ◽  
Community Analysis ◽  
Catalytic Subunit ◽  
Regulatory Subunit ◽  
Allosteric Communication ◽  
Dynamics Simulations ◽  
A Site ◽  
Kinase A

The holoenzyme complex of protein kinase A is in an inactive state; activation involves ordered cAMP binding to two tandem domains of the regulatory subunit and release of the catalytic subunit. Deactivation has been less studied, during which the two cAMPs unbind from the regulatory subunit to allow association of the catalytic subunit to reform the holoenzyme complex. Unbinding of the cAMPs appears ordered as indicated by a large difference in unbinding rates from the two sites, but the cause has remained elusive given the structural similarity of the two tandem domains. Even more intriguingly, NMR data show that allosteric communication between the two domains is unidirectional. Here, we present a mechanism for the unidirectionality, developed from extensive molecular dynamics simulations of the tandem domains in different cAMP-bound forms. Disparate responses to cAMP releases from the two sites (A and B) in conformational flexibility and chemical shift perturbation confirmed unidirectional allosteric communication. Community analysis revealed that the A-site cAMP, by forming across-domain interactions, bridges an essential pathway for interdomain communication. The pathway is impaired when this cAMP is removed but remains intact when only the B-site cAMP is removed. Specifically, removal of the A-site cAMP leads to the separation of the two domains, creating room for binding the catalytic subunit. Moreover, the A-site cAMP, by maintaining interdomain coupling, retards the unbinding of the B-site cAMP and stalls an unproductive pathway of cAMP release. Our work expands the perspective on allostery and implicates functional importance for the directionality of allostery.

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 ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Regulatory Subunit ◽  
Solution Structures ◽  
Kinase A

Alterations in protein kinase A signalling and cleft palate: a review

2005 ◽  
Vol 24 (5) ◽  
pp. 235-242 ◽  
Author(s):  
Chada S Reddy
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cellular Responses ◽  
Regulatory Subunit ◽  
Inhibitory Influence ◽  
Promoter Element ◽  
Secalonic Acid D ◽  
Secondary Palate ◽  
Kinase A

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.

Sign in / Sign up

Export Citation Format

Share Document