NGF-activated protein tyrosine phosphatase 1B mediates the phosphorylation and degradation of I-kappa-Balpha coupled to NF-kappa-B activation, thereby controlling dendrite morphology

Molecular and Cellular Neurosciences
Pedro J ChacónAlfredo Rodríguez Tébar

Abstract

NGF diminishes dendrite complexity in cultured hippocampal neurons by decreasing the number of primary and secondary dendrites, while increasing the length of those that remain. The transduction pathway used by NGF to provoke dendrite elongation involves the activation of NF-kappa-B and the expression of the homologues of Enhancer-of-split 1 gene. Here, we define important steps that link NGF with NF-kappa-B activation, through the activity of protein tyrosine phosphatase 1B (PTP1B). Binding of NGF to p75(NTR) stimulates PTP1B activity, which can be blocked by either pharmacological inhibition of the phosphatase or by transfecting neurons with a dn PTP1B isoform, whereby NGF is no longer able to stimulate dendrite growth. Indeed, overexpressing PTP1B alone provoked dendrite growth and further studies revealed a role for the src kinase downstream of PTP1B. Again, loss of src activity largely cancelled out the capacity of NGF to promote dendrite growth, whereas overexpression of v-src in neurons was sufficient to promote dendrite growth. Finally, the NGF/p75(NTR)/PTP1B/src kinase pathway led to the tyrosine phosphorylation of I-kappa-Balpha prior to its degradation, an event that is necessary for NF-kappa-B activation. Indeed, th...Continue Reading

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Citations

Nov 8, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Panos RoussosVahram Haroutunian
Mar 8, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David H QuachWarren G Tourtellotte
Nov 22, 2014·European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·Ting-Hsien KaoHerng-Sheng Lee
Jun 15, 2013·The International Journal of Biochemistry & Cell Biology·Sean J Crampton, Gerard W O'Keeffe
Dec 24, 2014·Neurobiology of Aging·Pedro J ChacónAlfredo Rodríguez-Tébar
Feb 23, 2019·Neurologia Medico-chirurgica·Takanori NozawaAkiyoshi Kakita
Nov 23, 2010·Reviews in the Neurosciences·Felicia Yu Hsuan Teng, Bor Luen Tang

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