Source:http://linkedlifedata.com/resource/pubmed/id/20972263
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
53
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pubmed:dateCreated |
2010-12-27
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pubmed:abstractText |
The protein kinase C (PKC)-MAPK signaling cascade is activated and is essential for viability when cells are starved for the phospholipid precursor inositol. In this study, we report that inhibiting inositol-containing sphingolipid metabolism, either by inositol starvation or treatment with agents that block sphingolipid synthesis, triggers PKC signaling independent of sphingoid base accumulation. Under these same growth conditions, a fluorescent biosensor that detects the necessary PKC signaling intermediate, phosphatidylinositol (PI)-4-phosphate (PI4P), is enriched on the plasma membrane. The appearance of the PI4P biosensor on the plasma membrane correlates with PKC activation and requires the PI 4-kinase Stt4p. Like other mutations in the PKC-MAPK pathway, mutants defective in Stt4p and the PI4P 5-kinase Mss4p, which generates phosphatidylinositol 4,5-bisphosphate, exhibit inositol auxotrophy, yet fully derepress INO1, encoding inositol-3-phosphate synthase. These observations suggest that inositol-containing sphingolipid metabolism controls PKC signaling by regulating access of the signaling lipids PI4P and phosphatidylinositol 4,5-bisphosphate to effector proteins on the plasma membrane.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Phosphatidylinositol 4-Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/STT4 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingolipids
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1083-351X
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
31
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pubmed:volume |
285
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
41947-60
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pubmed:meshHeading |
pubmed-meshheading:20972263-1-Phosphatidylinositol 4-Kinase,
pubmed-meshheading:20972263-Biosensing Techniques,
pubmed-meshheading:20972263-Cell Membrane,
pubmed-meshheading:20972263-Enzyme Activation,
pubmed-meshheading:20972263-Gene Expression Regulation, Fungal,
pubmed-meshheading:20972263-Inositol,
pubmed-meshheading:20972263-MAP Kinase Signaling System,
pubmed-meshheading:20972263-Phenotype,
pubmed-meshheading:20972263-Protein Kinase C,
pubmed-meshheading:20972263-Saccharomyces cerevisiae,
pubmed-meshheading:20972263-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:20972263-Signal Transduction,
pubmed-meshheading:20972263-Sphingolipids,
pubmed-meshheading:20972263-Temperature,
pubmed-meshheading:20972263-Time Factors
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pubmed:year |
2010
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pubmed:articleTitle |
Interruption of inositol sphingolipid synthesis triggers Stt4p-dependent protein kinase C signaling.
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pubmed:affiliation |
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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