Y. Levkovitz et al., Blockade of NGF-induced neurite outgrowth by a dominant-negative inhibitorof the Egr family of transcription regulatory factors, J NEUROSC, 21(1), 2001, pp. 45-52
Although it is well established that members of the Egr family of transcrip
tion regulatory factors are induced in many neuronal plasticity paradigms,
it is still unclear what role, if any, they play in this process. Because N
GF stimulation of pheochromocytoma 12 cells elicits a robust induction of E
gr family members, we have investigated their role in mediating long-term e
ffects elicited by NGF in these cells by using the Egr zinc finger DNA-bind
ing domain as a selective antagonist of Egr family-mediated transcription.
We report that expression of this Egr inhibitor construct suppresses neurit
e outgrowth elicited by NGF but not by dibutyryl cAMP. To check that this E
gr inhibitor construct does not act by blocking the MEK/ERK pathway, which
is known to mediate NGF-induced neurite outgrowth, we confirmed that the Eg
r inhibitor construct does not block NGF activation of Elk1-mediated transc
ription, a response that is dependent on this pathway. Conversely, inhibiti
on of MEK does not impair Egr family-mediated transcription. Thus, we concl
ude (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 bot
h are required to trigger neurite outgrowth induced by NGF.