Sphingosine Kinase 2 Is a Nuclear Protein and Inhibits DNA Synthesis

摘要: Sphingosine kinase-1 (SPHK1) is a key enzyme catalyzing the formation of an important bioactive lipid messenger, sphingosine 1-phosphate, and implicated in regulation cell proliferation antiapoptotic processes. Biological features another isozyme SPHK2, however, remain unclear. The present studies were undertaken to characterize SPHK2 by comparison with SPHK1. When was transiently expressed various lines, it localized nuclei as well cytosol, whereas SPHK1 distributed cytosol but not nucleus. We have mapped functional nuclear localization signal (NLS) N-terminal region SPHK2. observed that expression types causes inhibition DNA synthesis, resulting cycle arrest at G1/S phase. also demonstrated NLS mutant SPHK2R93E/R94E, failed enter nucleus inhibit synthesis. Moreover, fusion protein, NLS-SPHK1, where fused sequence acquired ability inhibited These results indicate localizes this may affect subsequent cellular events.