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FK506 potentiates NGF‐induced neurite outgrowth via the Ras/Raf/MAP kinase pathway
Author(s) -
Price Raymond D,
Yamaji Takayuki,
Matsuoka Nobuya
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705522
Subject(s) - neurite , microbiology and biotechnology , ly294002 , phospholipase c , neurotrophin , nerve growth factor , phosphatidylinositol , mapk/erk pathway , mitogen activated protein kinase , map kinase kinase kinase , signal transduction , kinase , biology , ask1 , chemistry , mitogen activated protein kinase kinase , protein kinase c , biochemistry , receptor , in vitro
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