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The Journal of Neuroscience, September 5, 2007, 27(36):9664-9669; doi:10.1523/JNEUROSCI.0608-07.2007

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Brief Communications
Nuclear Factor-B Activation via Tyrosine Phosphorylation of Inhibitor B- Is Crucial for Ciliary Neurotrophic Factor-Promoted Neurite Growth from Developing Neurons

Denis Gallagher,¹ Humberto Gutierrez,¹ Nuria Gavalda,¹ Gerard O'Keeffe,¹ Ron Hay,² and Alun M. Davies¹

¹School of Biosciences, Cardiff CF10 3US, United Kingdom, and ²School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom

Correspondence should be addressed to Alun M. Davies at the above address. Email: daviesalun{at}cf.ac.uk

The cytokine ciliary neurotrophic factor (CNTF) promotes the growth of neural processes from many kinds of neurons in the developing and regenerating adult nervous system, but the intracellular signaling mechanisms mediating this important function of CNTF are poorly understood. Here, we show that CNTF activates the nuclear factor-B (NF-B) transcriptional system in neonatal sensory neurons and that blocking NF-B-dependent transcription inhibits CNTF-promoted neurite growth. Selectively blocking NF-B activation by the noncanonical pathway that requires tyrosine phosphorylation of inhibitor B- (IB-), but not by the canonical pathway that requires serine phosphorylation of IB-, also effectively inhibits CNTF-promoted neurite growth. CNTF treatment activates spleen tyrosine kinase (SYK) whose substrates include IB-. CNTF-induced SYK phosphorylation is rapidly followed by increased tyrosine phosphorylation of IB-, and blocking SYK activation or tyrosine phosphorylation of IB- prevents CNTF-induced NF-B activation and CNTF-promoted neurite growth. These findings demonstrate that NF-B signaling by an unusual activation mechanism is essential for the ability of CNTF to promote the growth of neural processes in the developing nervous system.

Key words: NF-B; neurite; CNTF; SYK; development; sensory neuron

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Received Feb. 12, 2007; revised June 18, 2007; accepted July 14, 2007.

Correspondence should be addressed to Alun M. Davies at the above address. Email: daviesalun{at}cf.ac.uk

This article has been cited by other articles:

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