Protein Scaffolds, Lipid Domains and Substrate Recognition in Protein Kinase C Function: Implications for Rational Drug Design

2008 ◽  
pp. 185-203 ◽  
Author(s):  
J. W. Walker
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Drug Design ◽  
Substrate Recognition ◽  
Rational Drug Design ◽  
Lipid Domains ◽  
Protein Scaffolds ◽  
Kinase C ◽  
Rational Drug

scholarly journals Phosphoinositides and phosphoinositide-utilizing enzymes in detergent-insoluble lipid domains.

1996 ◽  
Vol 7 (6) ◽  
pp. 843-851 ◽  
Author(s):  
H R Hope ◽  
L J Pike
Keyword(s):  
Signal Transduction ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Membrane Fraction ◽  
Mitogen Activated Protein Kinase ◽  
Low Density ◽  
Membrane Domains ◽  
Lipid Domains ◽  
Kinase C ◽  
Mitogen Activated Protein

Recent evidence has implicated caveolae/DIGs in various aspects of signal transduction, a process in which polyphosphoinositides play a central role. We therefore undertook a study to determine the distribution of phosphoinositides and the enzymes that utilize them in these detergent-insoluble domains. We report here that the polyphosphoinositide phosphatase, but not several other phosphoinositide-utilizing enzymes, is highly enriched in a low density, Triton-insoluble membrane fraction that contains caveolin. This fraction is also enriched in polyphosphoinositides, containing approximately one-fifth of the total cellular phosphatidylinositol (4,5)P2. Treatment of cells with the tumor-promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), did not alter the distribution of polyphosphoinositides or the polyphosphoinositide phosphatase. However, PMA treatment did lead to a decrease in the mitogen-activated protein kinase and actin present in these domains. PMA also induced the recruitment of protein kinase C alpha to the caveolae/DIGs fraction. These findings suggest that polyphosphoinositides, the polyphosphoinositide phosphatase and protein kinase C play an important role in the structure or function of detergent-insoluble membrane domains.

Activation of Protein Kinase C by Coexisting Diacylglycerol-Enriched and Diacylglycerol-Poor Lipid Domains†

Biochemistry ◽  
1997 ◽  
Vol 36 (20) ◽  
pp. 6141-6148 ◽  
Author(s):  
Anne K. Hinderliter ◽  
Andrew R. G. Dibble ◽  
Rodney L. Biltonen ◽  
Julianne J. Sando
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Lipid Domains ◽  
Kinase C

scholarly journals Tuning the signalling output of protein kinase C

2014 ◽  
Vol 42 (6) ◽  
pp. 1477-1483 ◽  
Author(s):  
Corina E. Antal ◽  
Alexandra C. Newton
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Dynamic Range ◽  
Second Messenger ◽  
Spatiotemporal Dynamics ◽  
Present Review ◽  
Protein Scaffolds ◽  
Precise Control ◽  
Kinase C ◽  
Allosteric Activator

Precise control of the amplitude of protein kinase C (PKC) signalling is essential for cellular homoeostasis, and disruption of this control leads to pathophysiological states such as cancer, neurodegeneration and diabetes. For conventional and novel PKC, this amplitude is meticulously tuned by multiple inputs that regulate the amount of enzyme in the cell, its ability to sense its allosteric activator diacylglycerol, and protein scaffolds that co-ordinate access to substrates. Key to regulation of the signalling output of most PKC isoenzymes is the ability of cytosolic enzyme to respond to the membrane-embedded lipid second messenger, diacylglycerol, in a dynamic range that prevents signalling in the absence of agonists but allows efficient activation in response to small changes in diacylglycerol levels. The present review discusses the regulatory inputs that control the spatiotemporal dynamics of PKC signalling, with a focus on conventional and novel PKC isoenzymes.

Sign in / Sign up

Export Citation Format

Share Document