Protein Phosphorylation during the Process of Prestalk-to-Stalk Conversion in Dictyostelium discoideum. (Dictyostelium discoideum/8-bromo cyclic AMP/stalk differentiation/protein kinase A/protein kinase inhibitor)

1993 ◽  
Vol 35 (5) ◽  
pp. 561-568
Author(s):  
Mineko Maeda ◽  
Yuzuru Kubohara
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Phosphorylation ◽  
Protein Kinase A ◽  
Dictyostelium Discoideum ◽  
Kinase Inhibitor ◽  
Protein Kinase Inhibitor ◽  
Kinase A

scholarly journals Protein Kinase Inhibitor Peptide as a Tool to Specifically Inhibit Protein Kinase A

2020 ◽  
Vol 11 ◽  
Author(s):  
Chong Liu ◽  
Ping Ke ◽  
Jingjing Zhang ◽  
Xiaoying Zhang ◽  
Xiongwen Chen
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Kinase Inhibitor ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Protein Kinase Inhibitor ◽  
The Body ◽  
Specific Method ◽  
Inhibitor Peptide ◽  
Kinase A

The protein kinase enzyme family plays a pivotal role in almost every aspect of cellular function, including cellular metabolism, division, proliferation, transcription, movement, and survival. Protein kinase A (PKA), whose activation is triggered by cyclic adenosine monophosphate (cAMP), is widely distributed in various systems and tissues throughout the body and highly related to pathogenesis and progression of various kinds of diseases. The inhibition of PKA activation is essential for the study of PKA functions. Protein kinase inhibitor peptide (PKI) is a potent, heat-stable, and specific PKA inhibitor. It has been demonstrated that PKI can block PKA-mediated phosphorylase activation. Since then, researchers have a lot of knowledge about PKI. PKI is considered to be the most effective and specific method to inhibit PKA and is widely used in related research. In this review, we will first introduce the knowledge on the activation of PKA and mechanisms related on the inhibitory effects of PKI on PKA. Then, we will compare PKI-mediated PKA inhibition vs. several popular methods of PKA inhibition.

Structural origins of AGC protein kinase inhibitor selectivities: PKA as a drug discovery tool

2012 ◽  
Vol 393 (10) ◽  
pp. 1121-1129 ◽  
Author(s):  
Espen Åberg ◽  
Bjarte Lund ◽  
Alexander Pflug ◽  
Osman A.B.S.M. Gani ◽  
Ulli Rothweiler ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Kinases ◽  
Kinase Inhibitor ◽  
Protein Kinase Inhibitor ◽  
Constitutive Activity ◽  
Inhibitor Selectivity ◽  
Kinase A

Abstract The era of structure-based protein kinase inhibitor design began in the early 1990s with the determination of crystal structures of protein kinase A (PKA, or cyclic AMP-dependent kinase). Although many other protein kinases have since been extensively characterized, PKA remains a prototype for studies of protein kinase active conformations. It serves well as a model for the structural properties of AGC subfamily protein kinases, clarifying inhibitor selectivity profiles. Its reliable expression, constitutive activity, simple domain structure, and reproducible crystallizability have also made it a useful surrogate for the discovery of inhibitors of both established and emerging AGC kinase targets.

scholarly journals Multi-state recognition pathway of the intrinsically disordered protein kinase inhibitor by protein kinase A

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Cristina Olivieri ◽  
Yingjie Wang ◽  
Geoffrey C Li ◽  
Manu V S ◽  
Jonggul Kim ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Nuclear Export ◽  
Kinase Inhibitor ◽  
Intrinsically Disordered Protein ◽  
Protein Kinase Inhibitor ◽  
State Recognition ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Kinase A

In the nucleus, the spatiotemporal regulation of the catalytic subunit of cAMP-dependent protein kinase A (PKA-C) is orchestrated by an intrinsically disordered protein kinase inhibitor, PKI, which recruits the CRM1/RanGTP nuclear exporting complex. How the PKA-C/PKI complex assembles and recognizes CRM1/RanGTP is not well understood. Using NMR, SAXS, fluorescence, metadynamics, and Markov model analysis, we determined the multi-state recognition pathway for PKI. After a fast binding step in which PKA-C selects PKI’s most competent conformations, PKI folds upon binding through a slow conformational rearrangement within the enzyme’s binding pocket. The high-affinity and pseudo-substrate regions of PKI become more structured and the transient interactions with the kinase augment the helical content of the nuclear export sequence, which is then poised to recruit the CRM1/RanGTP complex for nuclear translocation. The multistate binding mechanism featured by PKA-C/PKI complex represents a paradigm on how disordered, ancillary proteins (or protein domains) are able to operate multiple functions such as inhibiting the kinase while recruiting other regulatory proteins for nuclear export.

Protein kinase inhibitor β enhances the constitutive activity of G-protein-coupled zinc receptor GPR39

2014 ◽  
Vol 462 (1) ◽  
pp. 125-132 ◽  
Author(s):  
Zsuzsa Kovacs ◽  
Teresa Schacht ◽  
Ann-Kathrin Herrmann ◽  
Philipp Albrecht ◽  
Konstantinos Lefkimmiatis ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
G Protein ◽  
Inhibitory Activity ◽  
Kinase Inhibitor ◽  
Protein Kinase Inhibitor ◽  
Constitutive Activity ◽  
G Protein Coupled ◽  
Kinase A

Protein kinase A inhibitor β interacts with the G-protein-coupled zinc receptor GPR39 and increases its cytoprotective constitutive activity via Gα13, but has no effect on ligand-mediated activation of Gs and Gq regardless of its inhibitory activity on protein kinase A.

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