Blockade of NGF-induced neurite outgrowth by a dominant-negative inhibitor of the Egr family of transcription regulatory factors

Yechiel Levkovitz, Kevin J. O'Donovan, Jay M. Baraban

Research output: Contribution to journalArticlepeer-review

Abstract

Although it is well established that members of the Egr family of transcription regulatory factors are induced in many neuronal plasticity paradigms, it is still unclear what role, if any, they play in this process. Because NGF stimulation of pheochromocytoma 12 cells elicits a robust induction of Egr family members, we have investigated their role in mediating long-term effects elicited by NGF in these cells by using the Egr zinc finger DNA-binding domain as a selective antagonist of Egr family-mediated transcription. We report that expression of this Egr inhibitor construct suppresses neurite outgrowth elicited by NGF but not by dibutyryl cAMP. To check that this Egr inhibitor construct does not act by blocking the MEK/ERK pathway, which is known to mediate NGF-induced neurite outgrowth, we confirmed that the Egr inhibitor construct does not block NGF activation of Elk1-mediated transcription, a response that is dependent on this pathway. Conversely, inhibition of MEK does not impair Egr family-mediated transcription. Thus, we conclude (1) that induction of Egr family members and activation of the MEK/ERK pathway by NGF are mediated by separate signaling pathways and (2) that both are required to trigger neurite outgrowth induced by NGF.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalJournal of Neuroscience
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2001

Keywords

  • ERK
  • Egr1
  • MEK
  • NGF
  • PC12 cells
  • Zif268

ASJC Scopus subject areas

  • Neuroscience(all)

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