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Activation of the IκB kinase complex is sufficient for neuronal differentiation of PC12 cells
Author(s) -
Azoitei Ninel,
Wirth Thomas,
Baumann Bernd
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03148.x
Subject(s) - neurite , nerve growth factor , ectopic expression , microbiology and biotechnology , phosphorylation , biology , kinase , transcription factor , tyrosine kinase , iκb kinase , mutant , signal transduction , receptor , nf κb , cell culture , biochemistry , in vitro , gene , genetics
We examined the role of the IκB kinase complex in nerve growth factor (NGF)‐induced neuronal differentiation of PC12 cells. We showed that neurite outgrowth is accompanied by an activation of the IKK complex and a delayed elevation of NF‐κB‐dependent transcription. Ectopic expression of a constitutively active form of IKK2 but not of IKK1 promoted neurite outgrowth in the absence of NGF. In addition, increased expression of Bcl‐2 and Bcl‐xL and resistance to apoptosis upon serum withdrawal were found. The IKK2‐driven neurite outgrowth was not blocked by MEK1/2 and PI3K inhibitors but was repressed by the SN50 peptide suggesting that NF‐κB activation is critical for this differentiation process. Transdominant mutants of IκBα (32/36‐SS/AA) and IKK1 only marginally reduced NGF‐driven neuritogenesis. However, a dominant negative mutant of IKK2 or an IκBα protein lacking the complete N‐terminus was able to repress neuritogenesis. We also detected tyrosine phosphorylation of IκBα during differentiation. Consequently, PC12 cells expressing mutant IκBα (Y42F) show an impaired neuritogenesis. Furthermore, PC12 cells ectopically expressing p65 show almost no signs of neurite outgrowth which is, however, found to some extent in c‐Rel‐expressing cells. Our data suggest that NGF‐induced PC12 differentiation includes activation of IKK2 which may promote the release of c‐Rel‐containing dimers.