scholarly journals Comparative thermodynamic analysis of cyclic nucleotide binding to protein kinase A

2007 ◽  
Vol 388 (2) ◽  
Author(s):  
Daniela Moll ◽  
Sonja Schweinsberg ◽  
Christian Hammann ◽  
Friedrich W. Herberg
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Thermodynamic Analysis ◽  
Cyclic Nucleotide ◽  
Nucleotide Binding ◽  
Cyclic Nucleotide Binding ◽  
Kinase A

scholarly journals The Roles of the RIIβ Linker and N-terminal Cyclic Nucleotide-binding Domain in Determining the Unique Structures of the Type IIβ Protein Kinase A

2014 ◽  
Vol 289 (41) ◽  
pp. 28505-28512 ◽  
Author(s):  
Donald K. Blumenthal ◽  
Jeffrey Copps ◽  
Eric V. Smith-Nguyen ◽  
Ping Zhang ◽  
William T. Heller ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cyclic Nucleotide ◽  
Nucleotide Binding ◽  
Binding Domain ◽  
Nucleotide Binding Domain ◽  
Cyclic Nucleotide Binding ◽  
Cyclic Nucleotide Binding Domain ◽  
Kinase A

scholarly journals Mutations that prevent cyclic nucleotide binding to binding sites A or B of type I cyclic AMP-dependent protein kinase.

1988 ◽  
Vol 263 (33) ◽  
pp. 17397-17404
Author(s):  
D Ogreid ◽  
S O Døskeland ◽  
K B Gorman ◽  
R A Steinberg
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Cyclic Nucleotide ◽  
Binding Sites ◽  
Nucleotide Binding ◽  
Type I ◽  
Dependent Protein Kinase ◽  
Cyclic Nucleotide Binding ◽  
Dependent Protein

scholarly journals Dependence of Electrical Activity and Calcium Influx-Controlled Prolactin Release on Adenylyl Cyclase Signaling Pathway in Pituitary Lactotrophs

2006 ◽  
Vol 20 (9) ◽  
pp. 2231-2246 ◽  
Author(s):  
Arturo E. Gonzalez-Iglesias ◽  
Yonghua Jiang ◽  
Melanija Tomić ◽  
Karla Kretschmannova ◽  
Silvana A. Andric ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Adenylyl Cyclase ◽  
Guanylyl Cyclase ◽  
Cyclic Nucleotide ◽  
Action Potentials ◽  
Soluble Guanylyl Cyclase ◽  
Cgmp Production ◽  
Camp And Cgmp ◽  
Kinase A

Abstract Pituitary lactotrophs in vitro fire extracellular Ca2+-dependent action potentials spontaneously through still unidentified pacemaking channels, and the associated voltage-gated Ca2+ influx (VGCI) is sufficient to maintain basal prolactin (PRL) secretion high and steady. Numerous plasma membrane channels have been characterized in these cells, but the mechanism underlying their pacemaking activity is still not known. Here we studied the relevance of cyclic nucleotide signaling pathways in control of pacemaking, VGCI, and PRL release. In mixed anterior pituitary cells, both VGCI-inhibitable and -insensitive adenylyl cyclase (AC) subtypes contributed to the basal cAMP production, and soluble guanylyl cyclase was exclusively responsible for basal cGMP production. Inhibition of basal AC activity, but not soluble guanylyl cyclase activity, reduced PRL release. In contrast, forskolin stimulated cAMP and cGMP production as well as pacemaking, VGCI, and PRL secretion. Elevation in cAMP and cGMP levels by inhibition of phosphodiesterase activity was also accompanied with increased PRL release. The AC inhibitors attenuated forskolin-stimulated cyclic nucleotide production, VGCI, and PRL release. The cell-permeable 8-bromo-cAMP stimulated firing of action potentials and PRL release and rescued hormone secretion in cells with inhibited ACs in an extracellular Ca2+-dependent manner, whereas 8-bromo-cGMP and 8-(4-chlorophenyltio)-2′-O-methyl-cAMP were ineffective. Protein kinase A inhibitors did not stop spontaneous and forskolin-stimulated pacemaking, VGCI, and PRL release. These results indicate that cAMP facilitates pacemaking, VGCI, and PRL release in lactotrophs predominantly in a protein kinase A- and Epac cAMP receptor-independent manner.

scholarly journals Mutations of PKA cyclic nucleotide-binding domains reveal novel aspects of cyclic nucleotide selectivity

2017 ◽  
Vol 474 (14) ◽  
pp. 2389-2403 ◽  
Author(s):  
Robin Lorenz ◽  
Eui-Whan Moon ◽  
Jeong Joo Kim ◽  
Sven H. Schmidt ◽  
Banumathi Sankaran ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Nucleotide ◽  
Molecular Basis ◽  
Nucleotide Binding ◽  
Effector Proteins ◽  
Regulatory Subunit ◽  
Dependent Protein Kinase ◽  
Cyclic Nucleotide Binding ◽  
Arginine Residues ◽  
Dependent Protein

Cyclic AMP and cyclic GMP are ubiquitous second messengers that regulate the activity of effector proteins in all forms of life. The main effector proteins, the 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and the 3′,5′-cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG), are preferentially activated by cAMP and cGMP, respectively. However, the molecular basis of this cyclic nucleotide selectivity is still not fully understood. Analysis of isolated cyclic nucleotide-binding (CNB) domains of PKA regulatory subunit type Iα (RIα) reveals that the C-terminal CNB-B has a higher cAMP affinity and selectivity than the N-terminal CNB-A. Here, we show that introducing cGMP-specific residues using site-directed mutagenesis reduces the selectivity of CNB-B, while the combination of two mutations (G316R/A336T) results in a cGMP-selective binding domain. Furthermore, introducing the corresponding mutations (T192R/A212T) into the PKA RIα CNB-A turns this domain into a highly cGMP-selective domain, underlining the importance of these contacts for achieving cGMP specificity. Binding data with the generic purine nucleotide 3′,5′-cyclic inosine monophosphate (cIMP) reveal that introduced arginine residues interact with the position 6 oxygen of the nucleobase. Co-crystal structures of an isolated CNB-B G316R/A336T double mutant with either cAMP or cGMP reveal that the introduced threonine and arginine residues maintain their conserved contacts as seen in PKG I CNB-B. These results improve our understanding of cyclic nucleotide binding and the molecular basis of cyclic nucleotide specificity.

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