Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720.

Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. Research Abstract Details 

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Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. Abstract Text:

Sphingosine-1-phosphate (S1P), a lipid signaling molecule that regulates many cellular functions, is synthesized from sphingosine and ATP by the action of sphingosine kinase. Two such kinases have been identified, SPHK1 and SPHK2. To begin to investigate the physiological functions of sphingosine kinase and S1P signaling, we generated mice deficient in SPHK1. Sphk1 null mice were viable, fertile, and without any obvious abnormalities. Total SPHK activity in most Sphk1-/-tissues was substantially, but not completely, reduced indicating the presence of multiple sphingosine kinases. S1P levels in most tissues from the Sphk1-/- mice were not markedly decreased. In serum, however, there was a significant decrease in the S1P level. Although S1P signaling regulates lymphocyte trafficking, lymphocyte distribution was unaffected in lymphoid organs of Sphk1-/- mice. The immunosuppressant FTY720 was phosphorylated and elicited lymphopenia in the Sphk1 null mice showing that SPHK1 is not required for the functional activation of this sphingosine analogue prodrug. The results with these Sphk1 null mice reveal that some key physiologic processes that require S1P receptor signaling, such as vascular development and proper lymphocyte distribution, can occur in the absence of SPHK1.

Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. Publishing Authors By Initials

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Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Journal of biological chemistry

VOLUME: 279

Page Numbers: 52487-92

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 30

MONTH: 09

YEAR: 2004

Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. Keywords Mesh Terms:

KEYWORDS: Sphingosine

MESH TERMS: metabolism

Chemical & Substance for Abstract: Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. Information

Substance Name: sphingosine kinase

Registry Number: EC 2.7.1.-

Grant and Affiliation Information for Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720.

AFFILIATION: Genetics of Development and Disease Branch, NIDDK and NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA61774

ACRONYM: CA

MEDLINETA: J Biol Chem

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