scholarly journals Divergent Effects of PKC (Protein Kinase C) α in the Human and Animal Heart?

2018 ◽  
Vol 11 (3) ◽  
Author(s):  
Kate L. Weeks ◽  
Julie R. McMullen
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Kinase C ◽  
Pkc Protein Kinase C

Lifespan regulation of conventional protein kinase C isotypes

2007 ◽  
Vol 35 (5) ◽  
pp. 1043-1045 ◽  
Author(s):  
D. Carmena ◽  
A. Sardini
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Second Messengers ◽  
Therapeutic Strategies ◽  
Kinase C ◽  
Signalling Network ◽  
Pkc Protein Kinase C ◽  
Lifespan Regulation

Plasma membrane translocation, following allosteric binding of second messengers, initiates the signal transduction process mediated by cPKC [conventional PKC (protein kinase C)] isotypes. Mechanisms regulating the lifespan of the active enzyme such as its phosphorylation, internalization, dephosphorylation and degradation are key elements of the signalling network. The understanding of such mechanisms is essential for the design of therapeutic strategies targeting PKC isoenzymes.

Regulation of exocytosis by protein kinase C

2005 ◽  
Vol 33 (6) ◽  
pp. 1341-1344 ◽  
Author(s):  
A. Morgan ◽  
R.D. Burgoyne ◽  
J.W. Barclay ◽  
T.J. Craig ◽  
G.R. Prescott ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Types ◽  
Neuroendocrine Cells ◽  
Protein Targets ◽  
Site Specific ◽  
Regulated Exocytosis ◽  
Kinase C ◽  
Pkc Protein Kinase C

PKC (protein kinase C) has been known for many years to modulate regulated exocytosis in a wide variety of cell types. In neurons and neuroendocrine cells, PKC regulates several different stages of the exocytotic process, suggesting that these multiple actions of PKC are mediated by phosphorylation of distinct protein targets. In recent years, a variety of exocytotic proteins have been identified as PKC substrates, the best characterized of which are SNAP-25 (25 kDa synaptosome-associated protein) and Munc18. In the present study, we review recent evidence suggesting that site-specific phosphorylation of SNAP-25 and Munc18 by PKC regulates distinct stages of exocytosis.

Occupational hazards: allosteric regulation of protein kinases through the nucleotide-binding pocket

2011 ◽  
Vol 39 (2) ◽  
pp. 472-476 ◽  
Author(s):  
Angus J.M. Cameron
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Binding Pocket ◽  
Occupational Hazards ◽  
Kinase C ◽  
Competitive Inhibitors ◽  
Central Activity ◽  
Pkc Protein Kinase C ◽  
Significant Opportunity

Targeting the protein kinase ATP-binding pocket provides a significant opportunity for the treatment of disease. Recent studies have revealed a central activity-independent role for nucleotide pocket occupation in the allosteric behaviour of diverse kinases. Regulation of nucleotide pocket conformation with either nucleotides or ATP competitive inhibitors has revealed an added dimension to the targeting of kinases. In the present paper, using PKC (protein kinase C) as a paradigm, the liabilities and opportunities associated with the occupation of the nucleotide pocket are explored.

Protein kinases, from B to C

2007 ◽  
Vol 35 (5) ◽  
pp. 1013-1017 ◽  
Author(s):  
A.J. Cameron ◽  
M. De Rycker ◽  
V. Calleja ◽  
D. Alcor ◽  
S. Kjaer ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Experimental Evidence ◽  
Protein Kinases ◽  
Protein Kinase B ◽  
Regulatory Domains ◽  
Catalytic Domains ◽  
Kinase C ◽  
Pkc Protein Kinase C ◽  
Underlying Mechanisms

The PKB (protein kinase B) and PKC (protein kinase C) families display highly related catalytic domains that require a largely conserved series of phosphorylations for the expression of their optimum activities. However, in cells, the dynamics of these modifications are quite distinct. Based on experimental evidence, it is argued that the underlying mechanisms determining these divergent behaviours relate to the very different manner in which their variant regulatory domains interact with their respective catalytic domains. It is concluded that the distinct behaviours of PKB and PKC proteins are defined by the typical ground states of these proteins.

scholarly journals PKC (Protein Kinase C)-δ Modulates AT (Antithrombin) Signaling in Vascular Endothelial Cells

2020 ◽  
Vol 40 (7) ◽  
pp. 1748-1762
Author(s):  
Sumith R. Panicker ◽  
Indranil Biswas ◽  
Hemant Giri ◽  
Xiaofeng Cai ◽  
Alireza R. Rezaie
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Intracellular Signaling ◽  
Vascular Endothelial Cells ◽  
Dominant Negative ◽  
Vascular Endothelial ◽  
Kinase C ◽  
Pkc Protein Kinase C ◽  
Anti Inflammatory

Objective: Native and latent conformers of AT (antithrombin) induce anti-inflammatory and proapoptotic signaling activities, respectively, in vascular endothelial cells by unknown mechanisms. Synd-4 (syndecan-4) has been identified as a receptor that is involved in transmitting signaling activities of AT in endothelial cells. Approach and Results: In this study, we used flow cytometry, signaling assays, immunoblotting and confocal immunofluorescence microscopy to investigate the mechanism of the paradoxical signaling activities of high-affinity heparin (native) and low-affinity heparin (latent) conformers of AT in endothelial cells. We discovered that native AT binds to glycosaminoglycans on vascular endothelial cells via its heparin-binding D-helix to induce anti-inflammatory signaling responses by recruiting PKC (protein kinase C)-δ to the plasma membrane and promoting phosphorylation of the Synd-4 cytoplasmic domain at Ser179. By contrast, the binding of latent AT to endothelial cells to a site(s), which is not competed by the native AT, induces a proapoptotic effect by localizing PKC-δ to the perinuclear/nuclear compartment in endothelial cells. Overexpression of a dominant-negative form of PKC-δ resulted in inhibition of anti-inflammatory and proapoptotic signaling activities of both native and latent AT. Conclusions: These results indicate that the native and latent conformers of AT may exert their distinct intracellular signaling effects through differentially modulating the subcellular localization of PKC-δ in endothelial cells.

scholarly journals Vasodilator-stimulated phosphoprotein (VASP) is phosphorylated on Ser157 by protein kinase C-dependent and -independent mechanisms in thrombin-stimulated human platelets

2005 ◽  
Vol 393 (2) ◽  
pp. 555-564 ◽  
Author(s):  
James K. T. Wentworth ◽  
Giordano Pula ◽  
Alastair W. Poole
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Rho Kinase ◽  
Human Platelets ◽  
Pkc Inhibitor ◽  
Kinase C ◽  
Vasp Phosphorylation ◽  
Pkc Protein Kinase C ◽  
Phosphoinositide 3 Kinase ◽  
Camp And Cgmp

VASP (vasodilator-stimulated phosphoprotein) is an actin- and profilin-binding protein that is expressed in platelets at high levels and plays a major role in negatively regulating secretory and adhesive events in these cells. VASP is a major substrate for cAMP- and cGMP-regulated protein kinases and it has been shown to be directly phosphorylated on Ser157 by PKC (protein kinase C). In the present paper, we show that, in human platelets, VASP is phosphorylated by PKC on Ser157, but not Ser239, in response to phorbol ester stimulation, in a manner blocked by the PKC inhibitor BIM I (bisindolylmaleimide I). In response to thrombin, VASP was also phosphorylated on Ser157, but this response was only partially inhibited by BIM I, indicating PKC-dependent and -independent pathways to VASP phosphorylation by thrombin. Using inhibitors, we have ruled out the possibility that the PKC-independent pathway acts through guanylate cyclase generation of cGMP, or through a phosphoinositide 3-kinase-dependent kinase. Inhibition of Rho kinase, however, substantially reduced Ser157 VASP phosphorylation, and its effects were additive with BIM I. This implicates Rho kinase and PKC as the major kinases that phosphorylate VASP Ser157 in response to thrombin in platelets.

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