Phosphatidylcholine-dependent protein kinase C activation. Effects of <i>cis</i>-fatty acid and diacylglycerol on synergism, autophosphorylation and Ca2+-dependency

Chen, Shu Guang; Kulju, David; Halt, S.; Murakami, Kentaro

doi:10.1042/bj2840221

Cited by 20 publications

(5 citation statements)

References 41 publications

(19 reference statements)

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“…Unsaturated FAs reduce the L β -L R and L R -H II transition temperatures, whereas saturated FAs do not (22,73). Accordingly, several reports have shown that addition of unsaturated FAs strongly enhances DAG-induced PKC activity, although saturated FAs have little effect (24)(25)(26)(27)(28)(74)(75)(76). Thus, the PKC-activating properties of DAGs and FAs can be associated with the increased propensity for hexagonal phase formation.…”

Section: Discussionmentioning

confidence: 99%

“…It has been recently shown that the presence of esterified or free polyunsaturated fatty acids increases bilayer curvature strain (20,21) and reduces phase transition temperatures for the gel-to-liquid-crystalline 2 and bilayer-to-nonbilayer phase transitions (22,23). Also, unesterified unsaturated fatty acids (FAs) in combination with DAG greatly enhance PKC activity in a synergistic manner (24)(25)(26)(27)(28). This study was designed to investigate the role of the lipid bilayer structure in the mechanism of the synergistic activation of PKC by DAG and fatty acids using 2 H NMR and PKC activity assays.…”

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confidence: 99%

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Synergistic Effects of Diacylglycerols and Fatty Acids on Membrane Structure and Protein Kinase C Activity

Goldberg

Zidovetzki

1998

Biochemistry

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The synergistic effects of diacylglycerol (DAG) and fatty acid (FA) in activating protein kinase C have been investigated by correlating their individual and combined effects on enzymatic activity and on membrane structure in phosphatidylcholine/phosphatidylserine (4:1) lipid mixtures using a combination of specific enzymatic assays and 31P and 2H NMR. Addition of DAGs and unsaturated FAs to the bilayers synergistically increased the tendency of the lipids to form nonbilayer phases with a concomitant increase in PKC activity until a maximum was achieved. Further increases in the DAG/FA concentration led to the formation of the nonbilayer lipid phases under the conditions of the PKC activity assays and correlated with decreased activity. The nonbilayer lipid phases still supported PKC activity, although with less than 50% efficiency as compared with the bilayer lipids. Long-chain saturated FA increased DAG-induced PKC activity by causing a lateral phase separation of gel (Lbeta) and liquid-crystalline (Lalpha) domains. Due to the preferential partitioning of DAGs into liquid-crystalline domains, the local DAG concentration increased in these domains, leading to an increase in PKC activity. Because a wide range of lipophilic compounds is capable of altering curvature stress, and therefore the tendency for nonbilayer phase formation in cellular membranes, these compounds would be expected to modulate PKC activity and the activities of a number of other membrane-associated enzymes that are sensitive to biophysical properties of lipid membranes.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Synergistic Effects of Diacylglycerols and Fatty Acids on Membrane Structure and Protein Kinase C Activity

Goldberg

Zidovetzki

1998

Biochemistry

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“…In fact, non-lamellar (HII) phase propensity has been shown to be involved in the translocation of PKC from the cytosol to membranes, a phenomenon associated with enzyme activation [4,245]. On the other hand, some studies suggest that a specific interaction between PKC and PS occurs [246][247][248], although other studies have indicated that different anionic phospholipids [249], or even neutral phospholipids like PC [250], can also activate PKC. These works demonstrate the importance of PKC-lipid interactions in the activity of this enzyme, and have been related to the therapeutic activity of some drugs against cancer, such as Minerval [9,245].…”

Section: Protein Kinase Cmentioning

confidence: 99%

“…In addition to membrane phospholipids, cis-unsaturated fatty acids such as arachidonic, linoleic and oleic acid can also activate PKC independently from DAG [250,256,257]. These lipids increase the nonlamellar (HII) phase propensity of membranes [258], which in turn favours the translocation of PKC to membranes [4].…”

Section: Protein Kinase Cmentioning

confidence: 99%

Membranes: a meeting point for lipids, proteins and therapies

Escribá¹,

González-Ros²,

Goñi³

et al. 2008

J Cellular Molecular Medi

352

287

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Membranes constitute a meeting point for lipids and proteins. Not only do they define the entity of cells and cytosolic organelles but they also display a wide variety of important functions previously ascribed to the activity of proteins alone. Indeed, lipids have commonly been considered a mere support for the transient or permanent association of membrane proteins, while acting as a selective cell/organelle barrier. However, mounting evidence demonstrates that lipids themselves regulate the location and activity of many membrane proteins, as well as defining membrane microdomains that serve as spatio-temporal platforms for interacting signalling proteins. Membrane lipids are crucial in the fission and fusion of lipid bilayers and they also act as sensors to control environmental or physiological conditions. Lipids and lipid structures participate directly as messengers or regulators of signal transduction. Moreover, their alteration has been associated with the development of numerous diseases. Proteins can interact with membranes through lipid co-/post-translational modifications, and electrostatic and hydrophobic interactions, van der Waals forces and hydrogen bonding are all involved in the associations among membrane proteins and lipids. The present study reviews these interactions from the molecular and biomedical point of view, and the effects of their modulation on the physiological activity of cells, the aetiology of human diseases and the design of clinical drugs. In fact, the influence of lipids on protein function is reflected in the possibility to use these molecular species as targets for therapies against cancer, obesity, neurodegenerative disorders, cardiovascular pathologies and other diseases, using a new approach called membrane-lipid therapy.

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“…In fact, several lines of evidence suggest numerous types of interactions between cholinergic and dopaminergic transmission. PC is involved in the activation and regulation of protein kinase C [65], and protein kinases play important roles in dopamine receptor signaling [66]. Moreover, the ACh and DA systems are related at the cortical level [67], and DA as well as DA receptor agonists increase cortical excitability and restore central cholinergic transmission in AD [67,68].…”

Section: Discussionmentioning

confidence: 99%

Carriers of a common variant in the dopamine transporter gene have greater dementia risk, cognitive decline, and faster ventricular expansion

Roussotte

Gutman

Hibar

et al. 2014

Alzheimer's & Dementia

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Background Genetic variants in DAT1, the gene encoding the dopamine transporter protein (DAT), have been implicated in many brain disorders. In a recent case-control study of Alzheimer’s disease (AD), a regulatory polymorphism in DAT1 showed a significant association with the clinical stages of dementia. Methods We tested whether this variant was associated with increased AD risk, and with measures of cognitive decline and longitudinal ventricular expansion, in a large sample of elderly participants with genetic, neurocognitive, and neuroimaging data from the Alzheimer’s Disease Neuroimaging Initiative. Results The minor allele – previously linked with increased DAT expression in vitro – was More common in AD patients than in both individuals with mild cognitive impairment and Healthy elderly controls. The same allele was also associated with poorer cognitive performance and faster ventricular expansion, independently of diagnosis. Conclusion These results may be due to reduced dopaminergic transmission in carriers of the DAT1 mutation.

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Phosphatidylcholine-dependent protein kinase C activation. Effects of cis-fatty acid and diacylglycerol on synergism, autophosphorylation and Ca2+-dependency

Cited by 20 publications

References 41 publications

Synergistic Effects of Diacylglycerols and Fatty Acids on Membrane Structure and Protein Kinase C Activity

Synergistic Effects of Diacylglycerols and Fatty Acids on Membrane Structure and Protein Kinase C Activity

Membranes: a meeting point for lipids, proteins and therapies

Carriers of a common variant in the dopamine transporter gene have greater dementia risk, cognitive decline, and faster ventricular expansion

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