Studies Suggesting the Participation of Protein Kinase A in 1,25(OH)2-Vitamin D3-Dependent Protein Phosphorylation in Cardiac Muscle

1998 ◽  
Vol 30 (2) ◽  
pp. 225-233 ◽  
Author(s):  
Graciela E. Santillán ◽  
Ricardo L. Boland
Keyword(s):  
Protein Kinase ◽  
Protein Phosphorylation ◽  
Cardiac Muscle ◽  
Protein Kinase A ◽  
Vitamin D3 ◽  
Dependent Protein ◽  
Kinase A

scholarly journals A Stapled Peptide Mimic of the Pseudosubstrate Inhibitor PKI Inhibits Protein Kinase A

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1567 ◽  
Author(s):  
Jascha T. Manschwetus ◽  
George N. Bendzunas ◽  
Ameya J. Limaye ◽  
Matthias J. Knape ◽  
Friedrich W. Herberg ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Kinase Inhibitor ◽  
Stapled Peptide ◽  
Peptide Mimic ◽  
Cellular Environment ◽  
Ic50 Values ◽  
Dependent Protein ◽  
Peptide Targeting ◽  
Kinase A

Kinases regulate multiple and diverse signaling pathways and misregulation is implicated in a multitude of diseases. Although significant efforts have been put forth to develop kinase-specific inhibitors, specificity remains a challenge. As an alternative to catalytic inhibition, allosteric inhibitors can target areas on the surface of an enzyme, thereby providing additional target diversity. Using cAMP-dependent protein kinase A (PKA) as a model system, we sought to develop a hydrocarbon-stapled peptide targeting the pseudosubstrate domain of the kinase. A library of peptides was designed from a Protein Kinase Inhibitor (PKI), a naturally encoded protein that serves as a pseudosubstrate inhibitor for PKA. The binding properties of these peptide analogs were characterized by fluorescence polarization and surface plasmon resonance, and two compounds were identified with KD values in the 500–600 pM range. In kinase activity assays, both compounds demonstrated inhibition with 25–35 nM IC50 values. They were also found to permeate cells and localize within the cytoplasm and inhibited PKA activity within the cellular environment. To the best of our knowledge, these stapled peptide inhibitors represent some of the highest affinity binders reported to date for hydrocarbon stapled peptides.

scholarly journals AniScan Using Extracellular Cyclic AMP-Dependent Protein Kinase A as a Serum Biomarker Assay for the Diagnosis of Malignant Tumors in Dogs

Sensors ◽  
2020 ◽  
Vol 20 (15) ◽  
pp. 4075
Author(s):  
Ji-Eun Lee ◽  
Woo-Jin Song ◽  
Hunjoo Lee ◽  
Byung-Gak Kim ◽  
Taeho Kim ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cancer Detection ◽  
Malignant Tumors ◽  
Cost Effective ◽  
Benign Tumors ◽  
Dependent Protein Kinase ◽  
Diagnostic Significance ◽  
Dependent Protein ◽  
Kinase A

The early detection of tumors improves chances of decreased morbidity and prolonged survival. Serum biomarkers are convenient to use and have several advantages over other approaches, such as accuracy and straightforward protocols. Reliable biomarkers from easily accessible sources are warranted for the development of cost-effective assays for routine screening, particularly in veterinary medicine. Extracellular c-AMP-dependent protein kinase A (ECPKA) is a cytosolic leakage enzyme. The diagnostic accuracy of detecting autoantibodies against ECPKA was found to be higher than that of ECPKA activity from enzymatic assays, which use a complicated method. Here, we investigated the diagnostic significance of measuring serum ECPKA autoantibody levels using an in-house kit (AniScan cancer detection kit; Biattic, Anyang, Korea). We used sera from 550 dogs, including healthy dogs and those with malignant and benign tumors. Serum ECPKA and immunoglobulin G were determined using the AniScan cancer detection kit. ECPKA autoantibody levels were significantly higher (p < 0.01) in malignant tumors than in benign tumors, non-tumor diseases, and healthy controls. On the basis of sensitivity and specificity values, AniScan ECPKA is a rapid and easy-to-use assay that can be applied to screen malignant tumors from benign tumors or other diseases in dogs.

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