Choline/ethanolamine kinase from mammalian tissues

Ishidate, Kozo

doi:10.1016/s0005-2760(97)00118-5

Cited by 74 publications

(50 citation statements)

References 42 publications

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“…We therefore hypothesize that PLD-mediated PC turnover is enhanced under salt stress. In such a way, the activation of CKs would be required for recycling the released Cho moieties into the CDPCho pathway, as in animals [42]. In contrast, no induction of phospholipase A 2 -mediated deacylation of PC was observed in response to either treatment because we failed to detect in vivo-labeled glycerophosphocholine nor a significant change in the labeled lyso-PC pool.…”

Section: Increased Ck Activity In Rosettes From Salt-stressedmentioning

confidence: 81%

“…Indeed, stimulated CK activity is required for recycling Cho into phospholipase D (PLD)-mediated PC turnover signaling pathways in mammals [42]. In yeast, a change in the phosphorylation state of CK directly affects the pool of PC, demonstrating that post-translational modifications of CK regulates PC synthesis through the CDPCho pathway [43].…”

Section: Ck Genes Are Up-regulated By Hyperosmotic Stressmentioning

confidence: 99%

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Regulation of phosphatidylcholine biosynthesis under salt stress involves choline kinases in Arabidopsis thaliana

TASSEVA¹

2004

FEBS Letters

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Increasing evidence suggests a major role for phosphatidylcholine (PC) in plant stress adaptation. The present work investigated the regulation of choline, PC and interconnected phosphatidylethanolamine biosynthesis in Arabidopsis thaliana L. as a function of cold-and salt-or mannitol-mediated hyperosmotic stresses. While PC synthesis is accelerated in both salt-and cold-treated plants, the choline kinase (CK) and phosphocholine cytidylyltransferase genes are oppositely regulated with respect to these abiotic treatments. Salt stress also stimulates CK activity in vitro. A possible regulatory role of CK in stimulating PC biosynthesis rate in salt-stressed plants is discussed.

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Section: Increased Ck Activity In Rosettes From Salt-stressedmentioning

confidence: 81%

Section: Ck Genes Are Up-regulated By Hyperosmotic Stressmentioning

confidence: 99%

Regulation of phosphatidylcholine biosynthesis under salt stress involves choline kinases in Arabidopsis thaliana

TASSEVA¹

2004

FEBS Letters

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“…It has been hypothesized that CHK activity plays a key role in the long term regulation of the Kennedy pathway, and CHK has been found to be inducible in various systems (16). Studies of mutant Chinese hamster ovary cells indicate that CHK is part of the control mechanism for the synthesis and degradation pathways that regulate the levels of PC (64).…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

mentioning

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

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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“…These enzymes are specific for ATP as the phosphate donor, but often can use both choline and ethanolamine as substrates. Enzymes that are specific for phosphorylation of ethanolamine are also known (11). Choline kinase can be regulatory for phosphatidylcholine biosynthesis under certain conditions (12).…”

mentioning

confidence: 99%

Identification of Critical Residues of Choline Kinase A2 from Caenorhabditis elegans

Yuan

Kent

2004

Journal of Biological Chemistry

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Choline kinase catalyzes the phosphorylation of choline by ATP, the first committed step in the CDP-choline pathway for phosphatidylcholine biosynthesis. To begin to elucidate the mechanism of catalysis by this enzyme, choline kinase A-2 from Caenorhabditis elegans was analyzed by systematic mutagenesis of highly conserved residues followed by analysis of kinetic and structural parameters. Specifically, mutants were analyzed with respect to K m and k cat values for each substrate and Mg 2؉ , inhibitory constants for Mg 2؉ and Ca 2؉ , secondary structure as monitored by circular dichroism, and sensitivity to unfolding in guanidinium hydrochloride. The most severe impairment of catalysis occurred with the modification of Asp-255 and Asn-260, which are located in the conserved Brenner's phosphotransferase motif, and Asp-301 and Glu-303, in the signature choline kinase motif. For example, mutation of Asp-255 or Asp-301 to Ala eliminated detectable catalytic activity, and mutation of Asn-260 and Glu-303 to Ala decreased k cat by 300-and 10-fold, respectively. Additionally, the K m for Mg 2؉ for mutants N260A and E303A was approximately 30-fold higher than that of wild type. Several other residues (Ser-86, Arg-111, Glu-125, and Trp-387) were identified as being important: Catalytic efficiencies (k cat /K m ) for the enzymes in which these residues were mutated to Ala were reduced to 2-25% of wild type. The high degree of structural similarity among choline kinase A-2, aminoglycoside phosphotransferases, and protein kinases, together with the results from this mutational analysis, indicates it is likely that these conserved residues are located at the catalytic core of choline kinase.

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Choline/ethanolamine kinase from mammalian tissues

Cited by 74 publications

References 42 publications

Regulation of phosphatidylcholine biosynthesis under salt stress involves choline kinases in Arabidopsis thaliana

Regulation of phosphatidylcholine biosynthesis under salt stress involves choline kinases in Arabidopsis thaliana

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

Identification of Critical Residues of Choline Kinase A2 from Caenorhabditis elegans

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