Immunosuppressant FK506 induces neurite outgrowth in PC12 mutant cells with impaired NGF-promoted neuritogenesis via a novel MAP kinase signaling pathway

Yoshio Kano, Tsutomu Nohno, Toru Hasegawa, Rei Takahashi, Fukumi Hiragami, Kenji Kawamura, Michael K. Iwama, Hirotoshi Motoda, Kanji Miyamoto

Research output: Contribution to journalArticle

11 Scopus citations

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 PC 12m3 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.

Original languageEnglish (US)
Pages (from-to)1655-1661
Number of pages7
JournalNeurochemical Research
Volume27
Issue number12
DOIs
StatePublished - Dec 1 2002

Keywords

  • FK506
  • MAP kinase
  • NGF
  • PC12 mutant cells

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Kano, Y., Nohno, T., Hasegawa, T., Takahashi, R., Hiragami, F., Kawamura, K., Iwama, M. K., Motoda, H., & Miyamoto, K. (2002). Immunosuppressant FK506 induces neurite outgrowth in PC12 mutant cells with impaired NGF-promoted neuritogenesis via a novel MAP kinase signaling pathway. Neurochemical Research, 27(12), 1655-1661. https://doi.org/10.1023/A:1021639128120