Regulation of CTP:phosphocholine cytidylyltransferase by amphitropism and relocalization

Cornell, Rosemary B.; Northwood, Ingrid C.

doi:10.1016/s0968-0004(00)01625-x

Cited by 196 publications

(187 citation statements)

References 53 publications

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“…However, the results would also be consistent with a model in which changes in phosphorylation occur secondarily to the change in intracellular localization. Such appears to be the case with CTP:phosphocholine cytidylyltransferase, which is dephosphorylated after becoming bound to membranes (33).…”

Section: Discussionmentioning

confidence: 99%

Insulin Controls Subcellular Localization and Multisite Phosphorylation of the Phosphatidic Acid Phosphatase, Lipin 1

Harris

Huffman

Chen

et al. 2007

Journal of Biological Chemistry

202

352

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Brain, liver, kidney, heart, and skeletal muscle from fatty liver dystrophy (fld/fld) mice, which do not express lipin 1 (lipin), contained much less Mg 2؉ -dependent phosphatidic acid phosphatase (PAP) activity than tissues from wild type mice. Lipin harboring the fld 2j (Gly 84 3 Arg) mutation exhibited relatively little PAP activity. These results indicate that lipin is a major PAP in vivo and that the loss of PAP activity contributes to the fld phenotype. PAP activity was readily detected in immune complexes of lipin from 3T3-L1 adipocytes, where the protein was found both as a microsomal form and a soluble, more highly phosphorylated, form. Fifteen phosphorylation sites were identified by mass spectrometric analyses. Insulin increased the phosphorylation of multiple sites and promoted a gel shift that was due in part to phosphorylation of Ser 106 . In contrast, epinephrine and oleic acid promoted dephosphorylation of lipin. The PAP-specific activity of lipin was not affected by the hormones or by dephosphorylation of lipin with protein phosphatase 1. However, the ratio of soluble to microsomal lipin was markedly increased in response to insulin and decreased in response to epinephrine and oleic acid. The results suggest that insulin and epinephrine control lipin primarily by changing localization rather than intrinsic PAP activity.

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Section: Discussionmentioning

confidence: 99%

Insulin Controls Subcellular Localization and Multisite Phosphorylation of the Phosphatidic Acid Phosphatase, Lipin 1

Harris

Huffman

Chen

et al. 2007

Journal of Biological Chemistry

202

352

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“…Transcriptional regulation of CCT is linked to cell cycle, cell growth, and differentiation, and CCT transcription is stimulated by ammonium ions and glycerol, the latter of which interlinks glycolysis with the Kennedy pathway (70). The regulation of CCT and its various isoforms has been extensively studied, and the reader is directed to the following reviews for further detailed information (35,68,71,72).…”

Section: The Ctp:phosphocholine Cytidylyltransferasementioning

confidence: 99%

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

2010

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SummaryThe glycerophospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE) account for greater than 50% of the total phospholipid species in eukaryotic membranes and thus play major roles in the structure and function of those membranes. In most eukaryotic cells, PC and PE are synthesized by an aminoalcoholphosphotransferase reaction, which uses sn-1,2-diradylglycerol and either CDP-choline or CDP-ethanolamine, respectively. This is the last step in a biosynthetic pathway known as the Kennedy pathway, so named after Eugene Kennedy who elucidated it over 50 years ago. This review will cover various aspects of the Kennedy pathway including: each of the biosynthetic steps, the functions and roles of the phospholipid products PC and PE, and how the Kennedy pathway has the potential of being a chemotherapeutic target against cancer and various infectious diseases. IUBMBIUBMB Life, 62(6): [414][415][416][417][418][419][420][421][422][423][424][425][426][427][428] 2010

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“…2A), Pct1p (or CCT in other organisms) is the rate-limiting enzyme. Pct1p/CCT is inactive in its soluble form but is activated upon binding to membranes (16,43). FHV infection increases transcription of the CCT-encoding Cct1 and Cct2 genes by ∼twofold (18).…”

Section: Virus-induced Local Synthesis And/or Accumulation Of Pc Is Amentioning

confidence: 99%

Positive-strand RNA viruses stimulate host phosphatidylcholine synthesis at viral replication sites

Zhang

Chukkapalli

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

112

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All positive-strand RNA viruses reorganize host intracellular membranes to assemble their viral replication complexes (VRCs); however, how these viruses modulate host lipid metabolism to accommodate such membrane proliferation and rearrangements is not well defined. We show that a significantly increased phosphatidylcholine (PC) content is associated with brome mosaic virus (BMV) replication in both natural host barley and alternate host yeast based on a lipidomic analysis. Enhanced PC levels are primarily associated with the perinuclear ER membrane, where BMV replication takes place. More specifically, BMV replication protein 1a interacts with and recruits Cho2p (choline requiring 2), a host enzyme involved in PC synthesis, to the site of viral replication. These results suggest that PC synthesized at the site of VRC assembly, not the transport of existing PC, is responsible for the enhanced accumulation. Blocking PC synthesis by deleting the CHO2 gene resulted in VRCs with wider diameters than those in wild-type cells; however, BMV replication was significantly inhibited, highlighting the critical role of PC in VRC formation and viral replication. We further show that enhanced PC levels also accumulate at the replication sites of hepatitis C virus and poliovirus, revealing a conserved feature among a group of positive-strand RNA viruses. Our work also highlights a potential broad-spectrum antiviral strategy that would disrupt PC synthesis at the sites of viral replication but would not alter cellular processes.positive-strand RNA viruses | viral replication complexes | virus-host interactions | virus control | phospholipids A ll positive-strand RNA viruses [(+)RNA viruses], which include numerous important human, animal, and plant pathogens, share similar strategies for genomic replication. A highly conserved and indispensable feature of their replication is the proliferation and reorganization of host cellular membranes to assemble viral replication complexes (VRCs). Despite this central importance, it is largely unknown how cellular membranes are rearranged by the viral replication proteins and how cellular lipid metabolism is modulated to accommodate membrane proliferation and remodeling.Brome mosaic virus (BMV) serves as a model for understanding VRC formation of (+)RNA viruses (1). BMV is the type member of the plant virus family Bromoviridae and a representative member of the alphavirus-like superfamily, which includes many human, animal, and plant-infecting viruses (2). BMV encodes two replication proteins, 1a and 2a pol . 2a pol serves as the replicase, whereas 1a has an N-terminal methyltransferase domain (3, 4) and a C-terminal ATPase/helicase-like domain (5). Together, 1a and 2a pol are necessary and sufficient for BMV replication. BMV induces vesicular structures in its surrogate host, the yeast Saccharomyces cerevisiae, and its natural host, barley (6, 7). These structures, termed spherules, have been shown to be the VRCs in yeast as 1a, 2a pol , and nascent viral RNAs reside in the interior of th...

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Regulation of CTP:phosphocholine cytidylyltransferase by amphitropism and relocalization

Cited by 196 publications

References 53 publications

Insulin Controls Subcellular Localization and Multisite Phosphorylation of the Phosphatidic Acid Phosphatase, Lipin 1

Insulin Controls Subcellular Localization and Multisite Phosphorylation of the Phosphatidic Acid Phosphatase, Lipin 1

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

Positive-strand RNA viruses stimulate host phosphatidylcholine synthesis at viral replication sites

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