Identification of functional nuclear export sequences in human sphingosine kinase 1.

Article Details

Citation

Inagaki Y, Li PY, Wada A, Mitsutake S, Igarashi Y

Identification of functional nuclear export sequences in human sphingosine kinase 1.

Biochem Biophys Res Commun. 2003 Nov 7;311(1):168-73.

PubMed ID
14575709 [ View in PubMed
]
Abstract

Sphingosine kinase (SPHK) is an enzyme that phosphorylates sphingosine to form sphingosine 1-phosphate (S1P). Human SPHK1 (hSPHK1) was localized predominantly in the cytoplasm when transiently expressed in Cos7 cells. In this study, we have found two functional nuclear export signal (NES) sequences in the middle region of hSPHK1. Deletion and mutagenesis studies revealed that the cytoplasmic localization of SPHK1 depends on its nuclear export, directed by the NES. Furthermore, upon treatment with leptomycin B, a specific inhibitor of the nuclear export receptor CRM1, a marked nuclear accumulation of hSPHK1 was observed, indicating that hSPHK1 shuttles between the cytoplasm and the nucleus. Our results provide the first evidence of the active nuclear export of SPHK1 and suggest it is mediated by a CRM1-dependent pathway.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Sphingosine kinase 1Q9NYA1Details