Title

The signal transduction pathway underlying ion channel gene regulation by SP1-C-Jun interactions

UMMS Affiliation

Brudnick Neuropsychiatric Research Institute

Publication Date

3-23-2001

Document Type

Article

Subjects

1-Phosphatidylinositol 3-Kinase; Animals; Binding Sites; Blotting, Western; Cell Differentiation; Cell Line; Drosophila; Ion Channels; MAP Kinase Signaling System; Mutation; Nerve Growth Factor; Neurons; PC12 Cells; Phenotype; Precipitin Tests; Promoter Regions (Genetics); Proto-Oncogene Proteins c-jun; Rats; Receptors, Cholinergic; *Signal Transduction; Sp1 Transcription Factor; Trans-Activation (Genetics); Transcription, Genetic; Transfection; ras Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

During neuronal differentiation, an exquisitely controlled program of signal transduction events takes place, leading to the temporally and spatially regulated expression of genes associated with the differentiated phenotype. A critical class of genes involved in this phenomenon is that made up of genes encoding neurotransmitter-gated ion channels that play a central role in signal generation and propagation within the nervous system. We used the well established PC12 cell line to investigate the molecular details underlying the expression of the neuronal nicotinic acetylcholine receptor class of ion channels. Neuronal differentiation of PC12 cells can be induced by nerve growth factor, leading to an increase in neuronal nicotinic acetylcholine receptor gene expression. Nerve growth factor initiates several signal transduction cascades. Here, we show that the Ras-dependent mitogen-activated protein kinase and phosphoinositide 3-kinase pathways are critical for the nerve growth factor-mediated increase in the transcriptional activity of a neuronal nicotinic acetylcholine receptor gene promoter. In addition, we show that a component of the Ras-dependent mitogen-activated protein kinase pathway, nerve growth factor-inducible c-Jun, exerts its effects on receptor gene promoter activity most likely through protein-protein interactions with Sp1. Finally, we demonstrate that the target for nerve growth factor signaling is an Sp1-binding site within the neuronal nicotinic acetylcholine receptor gene promoter.

Rights and Permissions

Citation: J Biol Chem. 2001 Jun 1;276(22):19040-5. Epub 2001 Mar 21. Link to article on publisher's site

DOI of Published Version

10.1074/jbc.M010735200

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

The Journal of biological chemistry

PubMed ID

11262397