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dc.contributor.authorZhou, Lihan
dc.contributor.authorStephanopoulos, Gregory
dc.contributor.authorToo, Heng-Phon
dc.contributor.authorSeow, Kok Huei
dc.date.accessioned2014-05-02T19:32:52Z
dc.date.available2014-05-02T19:32:52Z
dc.date.issued2013-12
dc.date.submitted2013-04
dc.identifier.issn1471-2202
dc.identifier.urihttp://hdl.handle.net/1721.1/86393
dc.description.abstractBackground: Synergistic multi-ligand treatments that can induce neuronal differentiation offer valuable strategies to regulate and modulate neurite outgrowth. Whereas the signaling pathways mediating single ligand-induced neurite outgrowth, such as Akt, extracellular signal-regulated kinase (Erk), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (P38), have been extensively studied, the mechanisms underlying multi-ligand synergistic neurite outgrowth are poorly understood. In an attempt to gain insight into synergistic neurite outgrowth, PC12 cells were treated with one of three combinations: pituitary adenylate cyclase-activating peptide (PACAP) with epidermal growth factor (EP), basic fibroblast growth factor (FP), or nerve growth factor (NP) and then challenged with the appropriate kinase inhibitors to assess the signaling pathways involved in the process. Results: Response surface analyses indicated that synergistic neurite outgrowth was regulated by distinct pathways in these systems. Synergistic increases in the phosphorylation of Erk and JNK, but not Akt or P38, were observed with the three growth factor-PACAP combinations. Unexpectedly, we identified a synergistic increase in JNK phosphorylation, which was involved in neurite outgrowth in the NP and FP, but not EP, systems. Inhibition of JNK using the SP600125 inhibitor reduced phosphorylation of 90 kDa ribosomal S6 kinase (P90RSK) in the NP and FP, but not EP, systems. This suggested the involvement of P90RSK in mediating the differential effects of JNK in synergistic neurite outgrowth. Conclusions: Taken together, these findings reveal the involvement of distinct signaling pathways in regulating neurite outgrowth in response to different synergistic growth factor-PACAP treatments. Our findings demonstrate a hitherto unrecognized mechanism of JNK-P90RSK in mediating synergistic neurite outgrowth induced by the co-treatment of growth factors and PACAP.en_US
dc.description.sponsorshipSingapore-MIT Allianceen_US
dc.publisherBioMed Central Ltden_US
dc.relation.isversionofhttp://dx.doi.org/10.1186/1471-2202-14-153en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_US
dc.sourceBioMed Central Ltden_US
dc.titlec-Jun N-terminal kinase in synergistic neurite outgrowth in PC12 cells mediated through P90RSKen_US
dc.typeArticleen_US
dc.identifier.citationSeow, Kok et al. “C-Jun N-Terminal Kinase in Synergistic Neurite Outgrowth in PC12 Cells Mediated through P90RSK.” BMC Neuroscience 14.1 (2013): 153.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.mitauthorStephanopoulos, Gregoryen_US
dc.relation.journalBMC Neuroscienceen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2014-04-05T12:18:17Z
dc.language.rfc3066en
dc.rights.holderKok Huei Seow et al.; licensee BioMed Central Ltd.
dspace.orderedauthorsSeow, Kok; Zhou, Lihan; Stephanopoulos, Gregory; Too, Heng-Phonen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-6909-4568
mit.licensePUBLISHER_CCen_US


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