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A Peptide Antagonist of ErbB Receptors, Inherbin3, Induces Neurite Outgrowth from Rat Cerebellar Granule Neurons Through ErbB1 Inhibition
Authors:Ruodan Xu  Stanislava Pankratova  Søren Hofman Christiansen  David Woldbye  Anne Højland  Elisabeth Bock  Vladimir Berezin
Affiliation:1. Laboratory of Neural Plasticity, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Symbion, Fruebjergvej 3, 2100, Copenhagen, Denmark
2. ENKAM Pharmaceuticals A/S, Copenhagen, Denmark
Abstract:
ErbB receptors not only function in cancer, but are also key developmental regulators in the nervous system. We previously identified an ErbB1 peptide antagonist, Inherbin3, that is capable of inhibiting tumor growth in vitro and in vivo. In this study, we found that inhibition of ErbB1 kinase activity and activation of ErbB4 by NRG-1β induced neurite extension, suggesting that ErbB1 and ErbB4 act as negative and positive regulators, respectively, of the neuritogenic response. Inherbin3, inhibited activation not only of ErbB1 but also of ErbB4 in primary neurons, strongly induced neurite outgrowth in rat cerebellar granule neurons, indicating that this effect mainly was due to inhibition of ErbB1 activation.
Keywords:
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