Phosphorylation of IκB-β is necessary for neuronal survival

Li Liu, Santosh R. D'Mello

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cerebellar granule neurons undergo apoptosis when switched from culture medium containing depolarizing levels of potassium (high potassium or HK) to nondepolarizing medium (low potassium or LK). We showed that in healthy neurons maintained in HK medium, IκB-β is phosphorylated at a novel site, Tyr-161. LK-induced neuronal apoptosis is accompanied by a decrease in the extent of IκB-β phosphorylation at this residue. Tyr-161 shares similarity to the consensus sequence for phosphorylation by the nonreceptor tyrosine kinases Abl and Arg. Arg phosphorylates Tyr-161 differentially in vitro, and LK treatment does cause a down-regulation of Arg activity. Moreover, treatment of neurons with two structurally distinct and highly selective Abl inhibitors, PD173955 and Gleevec, blocks HK-induced phosphorylation of IκB-β at Tyr-161 and induces neuronal apoptosis. Overexpression of wild-type IκB-β blocks LK-induced apoptosis, but this effect is abolished when Arg is pharmacologically inhibited. On the other hand, forced overexpression of IκB-β in which Tyr-161 is mutated inhibits survival in HK demonstrating the importance of this residue to neuronal survival. Phosphorylation of IκB-β enhances its association with p65/RelA causing an increase in NF-κB DNA binding activity. Our results identified IκB-β phosphorylation as a key event in neuronal survival and provided a mechanism by which this is mediated.

Original languageEnglish (US)
Pages (from-to)1506-1515
Number of pages10
JournalJournal of Biological Chemistry
Volume281
Issue number3
DOIs
StatePublished - Jan 20 2006

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Phosphorylation
Apoptosis
Neurons
Potassium
Consensus Sequence
Protein-Tyrosine Kinases
Culture Media
Down-Regulation
Association reactions
DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Phosphorylation of IκB-β is necessary for neuronal survival. / Liu, Li; D'Mello, Santosh R.

In: Journal of Biological Chemistry, Vol. 281, No. 3, 20.01.2006, p. 1506-1515.

Research output: Contribution to journalArticle

Liu, Li ; D'Mello, Santosh R. / Phosphorylation of IκB-β is necessary for neuronal survival. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 3. pp. 1506-1515.
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