title: p48 Ebp1 acts as a downstream mediator of Trk signaling in neurons, contributing neuronal differentiation.
abstract: Two Ebp1 isoproteins, p48 and p42, regulate cell survival and differentiation distinctively. Here we show that p48 is the major isoform in hippocampal neurons and is localized throughout the entire neuron. Notably, reduction of p48 Ebp1 expression inhibited BDNF-mediated neurite outgrowth in hippocampal neurons. The p48 protein acts as a downstream effector of the Trk receptor, which mediates the functions of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in hippocampal cells. Trk receptor activation by both NGF and BDNF induced phosphorylation of Ebp1 at the S360 upon the activation of protein kinase Cδ (PKCδ) and triggered dissociation of p48 from retinoblastoma (Rb). Although both NGF and BDNF activate mitogen-activated protein kinase (MAPK; extracellular signal-related kinase (ERK)) as well as phosphatidylinositide 3-kinase (PI3K)/Akt, their activation is regulated in different time-frame upon growth factor specificity, especially, eliciting PKCδ mediated p48 S360 phosphorylation. Thus, p48 Ebp1 contributes to neuronal cell differentiation and growth factor specificity through the activation of PKCδ, acting as a crucial downstream effector of neurotrophin signaling.
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Center for Molecular Medicine, Samsung Biomedical Research Institute, 300, Cheoncheon-dong Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Il-Sun
authors.initials: IS
authors.lastname: Kwon
authors.forename: Jee-Yin
authors.initials: JY
authors.lastname: Ahn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002461:Cell Line, Transformed; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D051381:Rats; D020917:Receptor, trkA / Q000819:agonists / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; C511885:PA2G4 protein, rat; D020033:Protein Isoforms; D016160:Retinoblastoma Protein; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D051744:Protein Kinase C-epsilon