Structure and function of choline kinase isoforms in mammalian cells

Aoyama, Chieko; Liao, Huanan; Ishidate, Kozo

doi:10.1016/j.plipres.2003.12.001

Cited by 200 publications

(200 citation statements)

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“…APEX1 (APEX nuclease 1), a multifunctional DNA repair enzyme, and MGMT (O-6-methylguanine-DNA methyltransferase), which repairs alkylated guanine in DNA, were up-regulated in our study. In addition, we observed the up-regulation of several genes, which are involved in stress response pathways, like the transcription factor DDIT3 (DNA-damage-inducible transcript 3), several heatshock proteins (HSPA5, HSP90AA1, HSP90B1, HSPB1) and CHKA (Choline kinase alpha) (Welch, 1992;Wang et al, 1996;Chen et al, 1998;Aoyama et al, 2004;van de Water et al 2006). Taken together these gene expression changes are judged to reflect a rather unspecific stress response.…”

Section: Oxidative Stress/ Dna Repair Mechanisms/ Stress Responsementioning

confidence: 79%

Identification of genes involved in gentamicin-induced nephrotoxicity in rats – A toxicogenomic investigation

Matheis

Gamber

et al. 2010

Experimental and Toxicologic Pathology

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To cite this version:N. Ozaki, K.A. Matheis, M. Gamber, T. Feidl, T. Nolte, et al.. Identification of genes involved in gentamicin induced nephrotoxicity in rats-a toxicogenomic investigation. Experimental and Toxicologic Pathology, Elsevier, 2010, 62 (5) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d m a n u s c r i p t

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Section: Oxidative Stress/ Dna Repair Mechanisms/ Stress Responsementioning

confidence: 79%

Identification of genes involved in gentamicin-induced nephrotoxicity in rats – A toxicogenomic investigation

Matheis

Gamber

et al. 2010

Experimental and Toxicologic Pathology

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“…For example, yeast cells contain two kinases with overlapping specificity: CK, with a specific activity 3.6-fold higher for choline than ethanolamine, and EK, with a specificity constant twofold higher for ethanolamine than for choline (40). Mammalian cells contain at least three isoforms of CK, encoded by two separate genes (CKa and CKb) (41), that are only active as homo-or heterodimers, but all display a preference for the substrate choline. They also have two ethanolamine-specific kinases: EK1 with negligible CK activity and EK2 with higher affinity for ethanolamine than choline (42).…”

Section: The Choline and Ethanolamine Kinasesmentioning

confidence: 99%

“…V max s range from 346 nmol/(min mg) for the yeast EK to 10.73 lmol/(min mg) for a soybean EK (40,41,(43)(44)(45)(46).…”

Section: The Choline and Ethanolamine Kinasesmentioning

confidence: 99%

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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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“…By positional cloning we have identified the molecular defect in rmd mutant mice as an intragenic deletion in the choline kinase beta (Chkb) gene, one of two mammalian choline kinase (CHK) enzymes (␣ and ␤). The monomeric CHK proteins combine to form the homo-or hetero-dimeric active forms (15) that catalyze the phosphorylation of choline to phosphocholine in the first committed step in the Kennedy pathway (the cytidine diphosphate (CDP)-choline pathway) for the biosynthesis of phosphatidylcholine (PC) (16). PC is the major phospholipid component of the eukaryotic plasma membrane external leaflet (17), an important precursor for many signaling molecules (18), and is thought to be essential for mammalian survival (19,20).…”

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confidence: 99%

A Rostrocaudal Muscular Dystrophy Caused by a Defect in Choline Kinase Beta, the First Enzyme in Phosphatidylcholine Biosynthesis

Sher

Aoyama

Huebsch

et al. 2006

Journal of Biological Chemistry

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109

102

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Muscular dystrophies include a diverse group of genetically heterogeneous disorders that together affect 1 in 2000 births worldwide. The diseases are characterized by progressive muscle weakness and wasting that lead to severe disability and often premature death. Rostrocaudal muscular dystrophy (rmd) is a new recessive mouse mutation that causes a rapidly progressive muscular dystrophy and a neonatal forelimb bone deformity. The rmd mutation is a 1.6-kb intragenic deletion within the choline kinase beta (Chkb) gene, resulting in a complete loss of CHKB protein and enzymatic activity. CHKB is one of two mammalian choline kinase (CHK) enzymes (␣ and ␤) that catalyze the phosphorylation of choline to phosphocholine in the biosynthesis of the major membrane phospholipid phosphatidylcholine. While mutant rmd mice show a dramatic decrease of CHK activity in all tissues, the dystrophy is only evident in skeletal muscle tissues in an unusual rostral-to-caudal gradient. Minor membrane disruption similar to dysferlinopathies suggest that membrane fusion defects may underlie this dystrophy, because severe membrane disruptions are not evident as determined by creatine kinase levels, Evans Blue infiltration, and unaltered levels of proteins in the dystrophin-glycoprotein complex. The rmd mutant mouse offers the first demonstration of a defect in a phospholipid biosynthetic enzyme causing muscular dystrophy, representing a unique model for understanding mechanisms of muscle degeneration.Muscular dystrophies are a variable class of more than 20 human disorders characterized by progressive muscle wasting and weakness resulting from myofiber degeneration and regeneration. Histologically, variation in myofiber size with centrally localized nuclei, fibrosis, and fatty infiltration are common features (1, 2). Despite their common pathologies, the genetic causes, severity, age of onset, and inheritance patterns vary widely among the dystrophies. The Muscular Dystrophy Association currently lists over 40 neuromuscular diseases as targets for its research programs and categorizes them by phenotypic characteristics such as age of onset, affected muscle groups, and inheritance pattern (Muscular Dystrophy Association, www.mdausa.org). In the last 10 years, the genetic mapping and identification of novel skeletal muscle genes, including cytoskeletal, cytosolic, nuclear membrane, sarcolemmal and extracellular matrix proteins, has dramatically changed this phenotype-based classification and provided clues as to the molecular basis of these disorders (3). What was once considered a single disease entity such as limb-girdle muscular dystrophy (LGMD) 4 has now been subdivided into seven different molecularly defined autosomal dominant (LGMD1A-1G) and ten autosomal recessive (LGMD2A-2J) diseases. Not surprisingly, many of these genes have converged to define pathways critical for the normal functioning and maintenance of skeletal muscles. The fact that many muscular dystrophy cases exist in which mutations to known dystrophy-causing genes have...

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Structure and function of choline kinase isoforms in mammalian cells

Cited by 200 publications

References 65 publications

Identification of genes involved in gentamicin-induced nephrotoxicity in rats – A toxicogenomic investigation

Identification of genes involved in gentamicin-induced nephrotoxicity in rats – A toxicogenomic investigation

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

A Rostrocaudal Muscular Dystrophy Caused by a Defect in Choline Kinase Beta, the First Enzyme in Phosphatidylcholine Biosynthesis

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