title: Immunosuppressant FK506 induces neurite outgrowth in PC12 mutant cells with impaired NGF-promoted neuritogenesis via a novel MAP kinase signaling pathway.
abstract: We obtained a drug-hypersensitive PC12 mutant cell (PC12m3), in which neurite outgrowth was strongly stimulated by various drugs such as FK506, calcimycin and cAMP, under the condition of NGF treatment. The frequency of neurite outgrowth stimulated by FK506 was approximately 40 times greater than by NGF alone. The effects of FK506 on neurite outgrowth in PC12m3 cells were inhibited by rapamycin, an FK506 antagonist, and by calcimycin, a calcium ionophore. PC12m3 cells had a strong NGF-induced MAP kinase activity, the same as PC12 parental cells. However, FK506-induced MAP kinase activity was detected only in PC12m3 cells. The activation of MAP kinase by FK506 in PC12m3 cells was markedly inhibited by rapamicin and calcimycin. FK506-induced MAP kinase activity was also inhibited by MAP kinase inhibitor U0126. These results demonstrate that drug-hypersensitive PC12m3 cells have a novel FK506-induced MAP kinase pathway for neuritogenesis.
authors.affiliation: Department of Health Science, Kibi International University, 8 Iga-machi Takahashi-city, Okayama 716-8508, Japan. yoshio@kiui.ac.jp
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kano
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nohno
authors.forename: Toru
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Rei
authors.initials: R
authors.lastname: Takahashi
authors.forename: Fukumi
authors.initials: F
authors.lastname: Hiragami
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawamura
authors.forename: Michael K
authors.initials: MK
authors.lastname: Iwama
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Motoda
authors.forename: Kanji
authors.initials: K
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D009154:Mutation; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; D020932:Nerve Growth Factor; D016559:Tacrolimus