Ras-signaling pathways: Positive and negative regulation of tau expression in PC12 cells

Einat Sadot, Hanna Jaaro, Rony Seger, Irith Ginzburg

Research output: Contribution to journalArticlepeer-review

Abstract

Tau is a microtubule-associated protein whose promoter is activated during the first phase of nerve growth factor-induced PC12 cell differentiation, whereas levels of its mRNA are accumulating throughout differentiation. In this study, we have followed the signal transduction cascades regulating tau induction. Using dominant negative Ras-expressing PC12 cells, we show that ras regulates tau expression during the first phase of PC12 cell differentiation. The ERK and JNK cascades, which are downstream of Ras, have opposing effects on tau promoter activity: ERK induces tau promoter activity, JNK inhibits it. Tau promoter activity in PC12 cells is correlated with a short-term activation of ERK, which declines after a few hours and is followed by an activation of the inhibitory JNK cascade 76 h later. These observations suggest that the induction end inhibition of tau promoter are mediated by alternate ERK and JNK activities, which may underlie a mechanism to turn on and off genes during PC12 cell differentiation.

Original languageEnglish (US)
Pages (from-to)428-431
Number of pages4
JournalJournal of Neurochemistry
Volume70
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

Keywords

  • Microtubule-associated protein kinase
  • PC12 cells
  • Promoter
  • Ras
  • Tau

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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