FK506 potentiates NGF-induced neurite outgrowth via the Ras/Raf/MAP kinase pathway
Article first published online: 2 FEB 2009
2003 British Pharmacological Society
British Journal of Pharmacology
Volume 140, Issue 5, pages 825–829, November 2003
How to Cite
Price, R. D., Yamaji, T. and Matsuoka, N. (2003), FK506 potentiates NGF-induced neurite outgrowth via the Ras/Raf/MAP kinase pathway. British Journal of Pharmacology, 140: 825–829. doi: 10.1038/sj.bjp.0705522
- Issue published online: 2 FEB 2009
- Article first published online: 2 FEB 2009
- (Received June 6, 2003, Revised August 29, 2003, Accepted September 1, 2003)
- neurite outgrowth
Nerve growth factor (NGF) and other members of the neurotrophin family are critical for the survival and differentiation of neurons within the peripheral and central nervous systems.
Neurophilin ligands, including FK506, potentiate NGF-induced neurite outgrowth in several experimental models, although the mechanism of this potentiation is unclear.
Therefore, we tested which signaling pathways were involved in FK506-potentiated neurite outgrowth in SH-SY5Y neuroblastoma cells using specific pharmacological inhibitors of various signaling molecules.
Inhibitors of Ras (lovastatin), Raf (GW5074), or MAP kinase (PD98059 and U0126) blocked FK506 activity, as did inhibitors of phospholipase C (U73122) and phosphatidylinositol 3′ kinase (LY294002).
Protein kinase C inhibitors (Go6983 and Ro31-8220) slightly but significantly inhibited neurite outgrowth, whereas inhibitors of p38 MAPK (SB203580) or c-Jun N-terminal kinase (SP600125) had no effect.
These data suggest that FK506 potentiates neurite outgrowth through the Ras/Raf/MAP kinase signaling pathway downstream of phospholipase C and phosphatidylinositol 3′ kinase.
British Journal of Pharmacology (2003) 140, 825–829. doi:10.1038/sj.bjp.0705522