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https://hdl.handle.net/2440/65973
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dc.contributor.author | Siow, D. | - |
dc.contributor.author | Anderson, C. | - |
dc.contributor.author | Berdyshev, E. | - |
dc.contributor.author | Skobeleva, A. | - |
dc.contributor.author | Natarajan, V. | - |
dc.contributor.author | Pitson, S. | - |
dc.contributor.author | Wattenberg, B. | - |
dc.contributor.editor | Cocco, L. | - |
dc.contributor.editor | Weber, G. | - |
dc.contributor.editor | Weber, C.E.F. | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Advances in Enzyme Regulation, 2011; 51(1):229-244 | - |
dc.identifier.issn | 0065-2571 | - |
dc.identifier.issn | 1873-2437 | - |
dc.identifier.uri | http://hdl.handle.net/2440/65973 | - |
dc.description.abstract | The sphingosine kinases (sphingosine kinase-1 and -2) have been implicated in a variety of physiological functions. Discerning their mechanism of action is complicated because in addition to producing the potent lipid second messenger sphingosine-1-phosphate, sphingosine kinases, both by producing sphingosine-1-phosphate and consuming sphingosine, have profound effects on sphingolipid metabolism. Sphingosine kinase-1 translocates to the plasma membrane upon agonist stimulation and this translocation is essential for the pro-oncogenic properties of this enzyme. Many of the enzymes of sphingolipid metabolism, including the enzymes that degrade sphingosine-1-phosphate, are membrane bound with restricted subcellular distributions. In the work described here we explore how subcellular localization of sphingosine kinase-1 affects the downstream metabolism of sphingosine-1-phosphate and the access of sphingosine kinase to its substrates. We find, surprisingly, that restricting sphingosine kinase to either the plasma membrane or the endoplasmic reticulum has a negligible effect on the rate of degradation of the sphingosine-1-phosphate that is produced. This suggests that sphingosine-1-phosphate is rapidly transported between membranes. However we also find that cytosolic or endoplasmic-reticulum targeted sphingosine kinase expressed at elevated levels produces extremely high levels of dihydrosphingosine-1-phosphate. Dihydrosphingosine is a proximal precursor in ceramide biosynthesis. Our data indicate that sphingosine kinase can divert substrate from the ceramide de novo synthesis pathway. However plasma membrane-restricted sphingosine kinase cannot access the pool of dihydrosphingosine. Therefore whereas sphingosine kinase localization does not affect downstream metabolism of sphingosine-1-phosphate, localization has an important effect on the pools of substrate to which this key signaling enzyme has access. | - |
dc.description.statementofresponsibility | Deanna L. Siow, Charles D. Anderson, Evgeny V. Berdyshev, Anastasia Skobeleva, Viswanathan Natarajan, Stuart M. Pitsong and Binks W. Wattenberg | - |
dc.description.uri | http://www.elsevier.com/wps/find/journaldescription.cws_home/427/description#description | - |
dc.language.iso | en | - |
dc.publisher | Elsevier Science Bv | - |
dc.rights | Copyright © 2011 Elsevier B.V. All rights reserved. SciVerse® is a registered trademark of Elsevier Properties S.A., | - |
dc.source.uri | http://dx.doi.org/10.1016/j.advenzreg.2010.09.004 | - |
dc.subject | Hela Cells | - |
dc.subject | Intracellular Membranes | - |
dc.subject | Humans | - |
dc.subject | Sphingosine | - |
dc.subject | Isoenzymes | - |
dc.subject | Phosphotransferases (Alcohol Group Acceptor) | - |
dc.subject | Lysophospholipids | - |
dc.subject | Sphingolipids | - |
dc.subject | Molecular Structure | - |
dc.subject | HEK293 Cells | - |
dc.title | Sphingosine kinase localization in the control of sphingolipid metabolism | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1016/j.advenzreg.2010.09.004 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Pitson, S. [0000-0002-9527-2740] | - |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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