Enhancement or induction of neurite formation by a protein tyrosine phosphatase inhibitor, 3,4-dephostatin, in growth factor-treated PC12h cells

Sari Fujiwara, Takumi Watanabe, Toshiharu Nagatsu, Jin Gohda, Masaya Imoto, Kazuo Umezawa

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We studied the effect of the 3,4 dihydroxy analogue of dephostatin (3,4-dephostatin), an inhibitor of protein-tyrosine phosphatase (PTPase), on the differentiation of rat pheochromocytoma PC12 cells. 3,4-Dephostatin accelerated NGF-induced neurite formation in PC12h cells, a subline of PC12 cells, whereas the inhibitor alone did not induce neurite formation. It sustained the NGF-induced tyrosine phosphorylation of several proteins, most prominently that of mitogen-activated protein (MAP) kinase. EGF alone did not induce differentiation in PC12h cells, but it induced neurite formation in the presence of 3,4-dephostatin. The inhibitor also prolonged EGF-induced tyrosine phosphorylation and activation of MAP kinase. An inactive analogue of dephostatin, 2'-O-methyl-dephostatin showed no effect on either neurite formation or MAP kinase tyrosine phosphorylation in NGF- or EGF-treated PC12h cells. Thus, we demonstrated that the PTPase inhibitor could enhance growth factor-induced differentiation in PC12 cells possibly by sustaining the MAP kinase activity.

Original languageEnglish
Pages (from-to)213-217
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume238
Issue number1
DOIs
Publication statusPublished - 1997 Sep 8

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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