Phosphorylation and Regulation of Choline Kinase fromSaccharomyces cerevisiae by Protein Kinase A

Kim, Kee Hong; Carman, George M.

doi:10.1074/jbc.274.14.9531

Cited by 39 publications

(36 citation statements)

References 48 publications

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“…PAH1 (S10D/S677D/S773D/S774D/S788D) derivative of pGH315 This study pGH315-7A PAH1 (S110A/S114A/S168A/S602A/T723A/S744A/S748A) derivative of pGH315 29 pGH315-S10A-7A PAH1 (S10A/S110A/S114A/S168A/S602A/T723A/S744A/S748A) derivative of pGH315 This study pGH315-S10D-7A PAH1 (S10D/S110A/S114A/S168A/S602A/T723A/S744A/S748A) derivative of pGH315 This study from yeast (60,(65)(66)(67). The in vitro phosphorylation was measured by following the incorporation of the radioactive phosphate of [␥-32 P]ATP into Pah1p ( Fig.…”

Section: Pka Phosphorylates Pah1p and Attenuates Its Pap Activity-mentioning

confidence: 99%

Protein Kinase A-mediated Phosphorylation of Pah1p Phosphatidate Phosphatase Functions in Conjunction with the Pho85p-Pho80p and Cdc28p-Cyclin B Kinases to Regulate Lipid Synthesis in Yeast

Han

Casciano

et al. 2012

Journal of Biological Chemistry

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139

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Background: Pah1p, a phosphatidate phosphatase in yeast, produces diacylglycerol for lipid synthesis. Results: Phosphorylation of Pah1p by protein kinase A inhibited membrane association, phosphatidate phosphatase activity, and triacylglycerol synthesis. Conclusion: Protein kinase A functioned in conjunction with Pho85p-Pho80p and Cdc28p-cyclin B kinases to regulate Pah1p. Significance: Lipid synthesis is regulated through multiple phosphorylations of Pah1p phosphatidate phosphatase.

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Section: Pka Phosphorylates Pah1p and Attenuates Its Pap Activity-mentioning

confidence: 99%

Protein Kinase A-mediated Phosphorylation of Pah1p Phosphatidate Phosphatase Functions in Conjunction with the Pho85p-Pho80p and Cdc28p-Cyclin B Kinases to Regulate Lipid Synthesis in Yeast

Han

Casciano

et al. 2012

Journal of Biological Chemistry

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139

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“…Although much work has been made in other organisms (Paddon et al 1982;Warden and Friedkin 1985;Kim and Carman 1999;Ramirez de Molina et al 2002;Yu et al 2002;Choi et al 2005;Soto 2008), little is known about human ChoKα regulation. It has been described that in HeLa cells, both EGF and insulin increase ChoK activity promoting the conversion of Cho to PCho, accompanied by an expansion of the PCho pool in treated cells (Uchida 1996).…”

Section: Chokα Regulationmentioning

confidence: 99%

CHKA (choline kinase alpha)

Ramírez¹,

Álvarez-Miranda²,

Jc³

2011

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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“…A recent study on the yeast Saccharomyces cerevisiae revealed that choline kinase is activated through phosphorylation by the Ras-cyclic adenosine monophosphate (cAMP) pathway (Kim and Carman, 1999). Choline kinase has also been found to be a substrate for yeast protein kinase A (PKA) (Kim and Carman, 1999). Increased levels of phosphocholine are found in mouse fibroblast cell lines transformed by H-Ras, v-Src and Mos but not c-Fos (Ratnam and Kent, 1995;Hernandez-Alcoceba et al, 1997).…”

mentioning

confidence: 99%

“…Despite its importance, little is known about the mechanisms that regulate choline kinase activity and hence phosphocholine production. A recent study on the yeast Saccharomyces cerevisiae revealed that choline kinase is activated through phosphorylation by the Ras-cyclic adenosine monophosphate (cAMP) pathway (Kim and Carman, 1999). Choline kinase has also been found to be a substrate for yeast protein kinase A (PKA) (Kim and Carman, 1999).…”

mentioning

confidence: 99%

Use of radiolabelled choline as a pharmacodynamic marker for the signal transduction inhibitor geldanamycin

et al. 2002

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There is an urgent need to develop non-invasive pharmacodynamic endpoints for the evaluation of new molecular therapeutics that inhibit signal transduction. We hypothesised that, when labelled appropriately, changes in choline kinetics could be used to assess geldanamycin pharmacodynamics, which involves inhibition of the HSP90 molecular chaperone?Raf1?Mitogenic Extracellular Kinase?Extracellular Signal-Regulated Kinase 1 and 2 signal transduction pathway. Towards identifying a potential pharmacodynamic marker response, we have studied radiolabelled choline metabolism in HT29 human colon carcinoma cells following treatment with geldanamycin. We studied the effects of geldanamycin, on net cellular accumulation of (methyl-14 C)choline and (methyl-14 C)phosphocholine production. In parallel experiments, the effects of geldanamycin on extracellular signal-regulated kinase 1 and 2 phosphorylation and cell viability were also assessed. Additional validation studies were carried out with the mitogenic extracellular kinase inhibitor U0126 as a positive control; a cyclin-dependent kinase-2 inhibitor roscovitine and the phosphatidylinositol 3-kinase inhibitor LY294002 as negative controls. Hemicholinium-3, an inhibitor of choline transport and choline kinase activity was included as an additional control. In exponentially growing HT29 cells, geldanamycin inhibited extracellular signal-regulated kinase 1 and 2 phosphorylation in a concentration-and time-dependent manner. These changes were associated with a reduction in (methyl-14 C)choline uptake, (methyl-14 C) phosphocholine production and cell viability. Brief exposure to U0126, suppressed phosphocholine production to the same extent as Hemicholinium-3. In contrast to geldanamycin and U0126, which act upstream of extracellular signalregulated kinase 1 and 2, roscovitine and LY294002 failed to suppress phosphocholine production. Our results suggest that when labelled with carbon-11 isotope, (methyl-11 C)choline may be a useful pharmacodynamic marker for the non-invasive evaluation of geldanamycin analogues.

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Phosphorylation and Regulation of Choline Kinase fromSaccharomyces cerevisiae by Protein Kinase A

Cited by 39 publications

References 48 publications

Protein Kinase A-mediated Phosphorylation of Pah1p Phosphatidate Phosphatase Functions in Conjunction with the Pho85p-Pho80p and Cdc28p-Cyclin B Kinases to Regulate Lipid Synthesis in Yeast

Protein Kinase A-mediated Phosphorylation of Pah1p Phosphatidate Phosphatase Functions in Conjunction with the Pho85p-Pho80p and Cdc28p-Cyclin B Kinases to Regulate Lipid Synthesis in Yeast

CHKA (choline kinase alpha)

Use of radiolabelled choline as a pharmacodynamic marker for the signal transduction inhibitor geldanamycin

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