Angiotensin stimulates phosphatidylcholine synthesis via a pathway involving diacylglycerol, protein kinase C, ERK1/2, and CTP:phosphocholine cytidylyltransferase

Kitos, Theresa E.; Choi, Chrystal M.Y.; Cornell, Rosemary B.

doi:10.1016/j.bbalip.2006.02.014

Cited by 4 publications

(4 citation statements)

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“…In both studies the inhibition of CCT could be partially reversed by exogenously supplied DAG, but not other lipid mediators, implying a primary role for DAG in the regulation of CCT by growth factors [16,188]. The stimulation of CCTa and PC synthesis by angiotensin or by exogenous DAG required functional protein kinase C and ERK1/2 [177]. Although CCTa activation was blunted by inhibitors of iPLA2, phospholipase C, and phospholipase D [16,188], the link between ERK1/2 activation and release of lipid activators of CCTa by phospholipases has yet to be fully established.…”

Section: Cct Relocalization And/or Activation In Response To Agents Tmentioning

confidence: 89%

“…The oxysterol/retinoic acid inhibition of PC synthesis depended on Ser-315 in CCTa, a potential ERK phosphorylation site that was previously shown to modulate CCTa affinity for membranes [169]. In a separate study using fibroblasts engineered with the angiotensin receptor, angiotensin activated CCTa and PC synthesis via a pathway dependent on ERK1/2, but no changes in CCT phosphorylation status were detected [177].…”

Section: Regulation By Phosphorylationmentioning

confidence: 95%

“…DAG and fatty acid enrichment cause changes in the phosphorylation status of the enzyme, which can also modulate membrane binding affinity. The promotion of CCT-membrane translocation by some proliferative signals depends on activation of a kinase network [177]. The critical factors responsible for a change in equilibrium between the soluble and membrane-bound form in a physiological setting are far from understood and may be context-sensitive.…”

Section: Ccta Mutations Responsible For Rare Genetic Diseasesmentioning

confidence: 99%

See 2 more Smart Citations

CTP:phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis

Cornell

Ridgway

2015

Progress in Lipid Research

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118

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Section: Cct Relocalization And/or Activation In Response To Agents Tmentioning

confidence: 89%

Section: Regulation By Phosphorylationmentioning

confidence: 95%

Section: Ccta Mutations Responsible For Rare Genetic Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

CTP:phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis

Cornell

Ridgway

2015

Progress in Lipid Research

Self Cite

118

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“…The active form of CT in cells is considered to be membrane-associated, whereas the soluble form is thought to be an inactive reservoir (5,6). Movement of CT to and from the membrane is linked to cell requirements for PC and is tightly regulated (7)(8)(9)(10)(11)(12)(13)(14). The lipid binding domain and the highly phosphorylated C terminus of CT are typically involved in regulating its activity.…”

mentioning

confidence: 99%

Inhibition of Hepatic Phosphatidylcholine Synthesis by 5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside Is Independent of AMP-activated Protein Kinase Activation

Jacobs

Lingrell

Dyck

et al. 2007

Journal of Biological Chemistry

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5-Aminoimidazole-4-carboxamide-1-␤-D-ribofuranoside (AICAr), a commonly used indirect activator of AMP-activated protein kinase (AMPK), inhibits phosphatidylcholine (PC) biosynthesis in freshly isolated hepatocytes. In all nucleated mammalian cells, PC is synthesized from choline via the Kennedy (CDP-choline) pathway. The purpose of our study was to provide direct evidence that AMPK regulates phospholipid biosynthesis and to elucidate the mechanism(s) by which AMPK inhibits hepatic PC synthesis. Incubations of hepatocytes with AICAr resulted in a dose-dependent activation of AMPK and inhibition of PC biosynthesis. Surprisingly, adenoviral delivery of constitutively active AMPK did not alter PC biosynthesis. In addition, expression of dominant negative mutants of AMPK was unable to block the AICAr-dependent inhibition of PC biosynthesis, indicating that AICAr was acting independently of AMPK activation. Determination of aqueous intermediates of the CDPcholine pathway indicated that choline kinase, the first enzyme in the pathway, was inhibited by AICAr administration. Flux through the CDP-choline pathway was directly correlated to the level of intracellular ATP concentrations. Therefore, it is possible that inhibition of PC biosynthesis is another process by which the cell can reduce ATP consumption in times of energetic stress. However, unlike cholesterol and triacylglycerol biosynthesis, PC production is not regulated by AMPK. Phosphatidylcholine (PC)4 is quantitatively the most important phospholipid in mammalian membranes, is the primary phospholipid in bile and in plasma lipoproteins, and is a precursor for the synthesis of sphingomyelin and phosphatidylserine. In nucleated cells, PC biosynthesis occurs via the Kennedy (CDP-choline) pathway. Choline kinase (CK), the enzyme catalyzing the first committed step in this pathway, phosphorylates choline to form phosphocholine. Choline kinase is not considered an important site in regulating PC biosynthesis (1-3); however, deletion of the CK␤ isoform results in muscular dystrophy in mice due to lack of PC in muscle (4). CTP:phosphocholine cytidylyltransferase (CT), which catalyzes the rate-limiting conversion of phosphocholine to CDPcholine (1-3), is the most extensively studied enzyme in the Kennedy pathway. CT is found in soluble cell and tissue extracts and bound to membranes. The active form of CT in cells is considered to be membrane-associated, whereas the soluble form is thought to be an inactive reservoir (5, 6). Movement of CT to and from the membrane is linked to cell requirements for PC and is tightly regulated (7-14). The lipid binding domain and the highly phosphorylated C terminus of CT are typically involved in regulating its activity. The last enzyme in the pathway, CDP-choline:1,2-diacylglycerol cholinephosphotransferase, is in excess in cells and thus does not determine the rate of PC biosynthesis. This reaction requires the availability of diacylglycerol, which is synthesized from fatty acids and glycerol.Hepatocytes are unique in that they can a...

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Membrane lipid compositional sensing by the inducible amphipathic helix of CCT

Cornell

2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Angiotensin stimulates phosphatidylcholine synthesis via a pathway involving diacylglycerol, protein kinase C, ERK1/2, and CTP:phosphocholine cytidylyltransferase

Cited by 4 publications

References 47 publications

CTP:phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis

CTP:phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis

Inhibition of Hepatic Phosphatidylcholine Synthesis by 5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside Is Independent of AMP-activated Protein Kinase Activation

Membrane lipid compositional sensing by the inducible amphipathic helix of CCT

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