Sphingosine kinase 1 is a critical component of the copper-dependent FGF1 export pathway |
| |
Authors: | Soldi Raffaella Mandinova Anna Venkataraman Krishnan Hla Timoty Vadas Mathew Pitson Stuart Duarte Maria Graziani Irene Kolev Vihren Kacer Doreen Kirov Aleksandr Maciag Thomas Prudovsky Igor |
| |
Institution: | Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA. |
| |
Abstract: | Sphingosine kinase 1 catalyzes the formation of sphingosine-1-phosphate, a lipid mediator involved in the regulation of angiogenesis. Sphingosine kinase 1 is constitutively released from cells, even though it lacks a classical signal peptide sequence. Because copper-dependent non-classical stress-induced release of FGF1 also regulates angiogenesis, we questioned whether sphingosine kinase 1 is involved in the FGF1 release pathway. We report that (i) the coexpression of sphingosine kinase 1 with FGF1 inhibited the release of sphingosine kinase 1 at 37 degrees C; (ii) sphingosine kinase 1 was released at 42 degrees C in complex with FGF1; (iii) sphingosine kinase 1 null cells failed to release FGF1 at stress; (iv) sphingosine kinase 1 is a high affinity copper-binding protein which formed a complex with FGF1 in a cell-free system, and (v) sphingosine kinase 1 over expression rescued the release of FGF1 from inhibition by the copper chelator, tetrathiomolybdate. We propose that sphingosine kinase 1 is a component of the copper-dependent FGF1 release pathway. |
| |
Keywords: | Sphingosine kinase 1 Fibroblast growth factor 1 Copper Non-classical release Angiogenesis |
本文献已被 ScienceDirect PubMed 等数据库收录! |