HA1004, an inhibitor of serine/threonine protein kinases, restores the sensitivity of thymic lymphomas to Ca2+-mediated apoptosis through a protein kinase A-independent mechanism

2002 ◽  
Vol 2 (4) ◽  
pp. 435-442 ◽  
Author(s):  
Janusz Matuszyk ◽  
Malgorzata Cebrat ◽  
Wojciech Kalas ◽  
Leon Strzadala
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Kinases ◽  
Independent Mechanism ◽  
Kinase A

Comparative Study of Active and Allosteric Interaction in Protein Kinases

2021 ◽  
Vol 8 (1) ◽  
pp. 23-31
Author(s):  
Jefrin Ahmed ◽  
Judith Mary Lamo ◽  
Baphilinia Jones Mylliemngap
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Kinases ◽  
Active Site ◽  
Cell Function ◽  
Binding Capacity ◽  
Second Messengers ◽  
Gene Families ◽  
Allosteric Site ◽  
Kinase A

Protein kinases are key regulators of cell function that constitute one of the largest and most functionally diverse gene families. By adding phosphate groups to substrate proteins, they direct the activity, localization and overall function of many proteins, and serve to orchestrate the activity of almost all cellular processes. The main protein kinases consist of protein kinase A (PKA), protein kinase B (PKB), and protein kinase C (PKC) and are distinguished from each other by the different intracellular second messengers involved in their regulation and by the selective substrates they use. They all have a binding site for Mg2+-ATP (phosphate donor) and for substrate protein as well as various regulatory sites. We formulated to compare the binding capacity of protein kinases at the active site to allosteric sites. By comparing the active site and allosteric site of the protein kinases – A, B and C, using molecular docking it was found that in most of the cases the binding energy is high when an inhibitor binds to an active site as compared to the allosteric site. This comparison gave us an understanding of the interaction and inhibition of compounds to protein kinases in order to inhibit the activity of protein kinase A, B and C. It was concluded that for inhibiting the protein kinase function such as cell division and proliferation, binding of inhibitor to the allosteric site will be more effective.

Protein Kinase A-Independent Mechanism of cAMP in Insulin Secretion

2008 ◽  
pp. 133-146
Author(s):  
Susumu Seino ◽  
Takashi Miki ◽  
Tadao Shibasaki
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Independent Mechanism ◽  
Kinase A

A-kinase-anchoring proteins and cytoskeletal signalling events

2003 ◽  
Vol 31 (1) ◽  
pp. 87-89 ◽  
Author(s):  
J.D. Scott
Keyword(s):  
Protein Kinase ◽  
Molecular Mass ◽  
Protein Kinase A ◽  
Protein Kinases ◽  
Recent Progress ◽  
Membrane Receptors ◽  
Anchoring Proteins ◽  
Syndrome Protein ◽  
Kinase A

Targeting of protein kinases and phosphatases to the cytoskeleton enhances the regulation of many signalling events. Cytoskeletal signalling complexes facilitate this process by optimizing the relay of messages from membrane receptors to specific sites on the actin cytoskeleton. These signals influence fundamental cell properties such as shape, movement and division. Targeting of the cAMP-dependent kinase (protein kinase A) and other enzymes to this compartment is achieved through interaction with A-kinase-anchoring proteins (AKAPs). The present paper discusses recent progress on dissecting the biological role of WAVE1 (Wiskott–Alrich syndrome protein family verprolin homology protein 1), an AKAP that assembles a cytoskeletal transduction complex in response to signals that emanate from the low-molecular-mass GTPase, Rac.

scholarly journals Potential Role for Protein Kinases in Regulation of Bidirectional Endoplasmic Reticulum-to-Golgi Transport Revealed by Protein Kinase Inhibitor H89

2000 ◽  
Vol 11 (8) ◽  
pp. 2577-2590 ◽  
Author(s):  
Tina H. Lee ◽  
Adam D. Linstedt
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Kinases ◽  
Potential Role ◽  
Kinase Inhibitor ◽  
Transport Processes ◽  
Protein Kinase Inhibitors ◽  
Er Export ◽  
Kinase A

Recent evidence suggests a regulatory connection between cell volume, endoplasmic reticulum (ER) export, and stimulated Golgi-to-ER transport. To investigate the potential role of protein kinases we tested a panel of protein kinase inhibitors for their effect on these steps. One inhibitor, H89, an isoquinolinesulfonamide that is commonly used as a selective protein kinase A inhibitor, blocked both ER export and hypo-osmotic-, brefeldin A-, or nocodazole-induced Golgi-to-ER transport. In contrast, H89 did not block the constitutive ER Golgi-intermediate compartment (ERGIC)-to-ER and Golgi-to-ER traffic that underlies redistribution of ERGIC and Golgi proteins into the ER after ER export arrest. Surprisingly, other protein kinase A inhibitors, KT5720 and H8, as well as a set of protein kinase C inhibitors, had no effect on these transport processes. To test whether H89 might act at the level of either the coatomer protein (COP)I or the COPII coat protein complex we examined the localization of βCOP and Sec13 in H89-treated cells. H89 treatment led to a rapid loss of Sec13-labeled ER export sites but βCOP localization to the Golgi was unaffected. To further investigate the effect of H89 on COPII we developed a COPII recruitment assay with permeabilized cells and found that H89 potently inhibited binding of exogenous Sec13 to ER export sites. This block occurred in the presence of guanosine-5′-O-(3-thio)triphosphate, suggesting that Sec13 recruitment is inhibited at a step independent of the activation of the GTPase Sar1. These results identify a requirement for an H89-sensitive factor(s), potentially a novel protein kinase, in recruitment of COPII to ER export sites, as well as in stimulated but not constitutive Golgi-to-ER transport.

scholarly journals N6-Substituted cAMP Analogs Inhibit bTREK-1 K+ Channels and Stimulate Cortisol Secretion by a Protein Kinase A-Independent Mechanism

2009 ◽  
Vol 76 (6) ◽  
pp. 1290-1301 ◽  
Author(s):  
Haiyan Liu ◽  
Judith A. Enyeart ◽  
John J. Enyeart
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Cortisol Secretion ◽  
K Channels ◽  
Independent Mechanism ◽  
Kinase A

scholarly journals Epac1 mediates protein kinase A–independent mechanism of forskolin-activated intestinal chloride secretion

2009 ◽  
Vol 187 (7) ◽  
pp. i18-i18
Author(s):  
Kazi Mirajul Hoque ◽  
Owen M. Woodward ◽  
Damian B. van Rossum ◽  
Nicholas C. Zachos ◽  
Linxi Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Chloride Secretion ◽  
Independent Mechanism ◽  
Intestinal Chloride Secretion ◽  
Kinase A

scholarly journals Discovery of cellular substrates for protein kinase A using a peptide array screening protocol

2011 ◽  
Vol 438 (1) ◽  
pp. 103-110 ◽  
Author(s):  
F. Donelson Smith ◽  
Bret K. Samelson ◽  
John D. Scott
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Kinases ◽  
Covalent Modification ◽  
Peptide Arrays ◽  
Post Translational Modification ◽  
Cellular Events ◽  
Screening Protocol ◽  
Full Complement ◽  
Kinase A

Post-translational modification of proteins is a universal form of cellular regulation. Phosphorylation on serine, threonine, tyrosine or histidine residues by protein kinases is the most widespread and versatile form of covalent modification. Resultant changes in activity, localization or stability of phosphoproteins drives cellular events. MS and bioinformatic analyses estimate that ~30% of intracellular proteins are phosphorylated at any given time. Multiple approaches have been developed to systematically define targets of protein kinases; however, it is likely that we have yet to catalogue the full complement of the phosphoproteome. The amino acids that surround a phosphoacceptor site are substrate determinants for protein kinases. For example, basophilic enzymes such as PKA (protein kinase A), protein kinase C and calmodulin-dependent kinases recognize basic side chains preceding the target serine or threonine residues. In the present paper we describe a strategy using peptide arrays and motif-specific antibodies to identify and characterize previously unrecognized substrate sequences for protein kinase A. We found that the protein kinases PKD (protein kinase D) and MARK3 [MAP (microtubule-associated protein)-regulating kinase 3] can both be phosphorylated by PKA. Furthermore, we show that the adapter protein RIL [a product of PDLIM4 (PDZ and LIM domain protein 4)] is a PKA substrate that is phosphorylated on Ser119 inside cells and that this mode of regulation may control its ability to affect cell growth.

Structural Analysis of ARC-Type Inhibitor (ARC-1034) Binding to Protein Kinase A Catalytic Subunit and Rational Design of Bisubstrate Analogue Inhibitors of Basophilic Protein Kinases

2009 ◽  
Vol 52 (2) ◽  
pp. 308-321 ◽  
Author(s):  
Darja Lavogina ◽  
Marje Lust ◽  
Indrek Viil ◽  
Norbert König ◽  
Gerda Raidaru ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Protein Kinases ◽  
Rational Design ◽  
Catalytic Subunit ◽  
Kinase A
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