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http://purl.uniprot.org/citations/16820412http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16820412http://www.w3.org/2000/01/rdf-schema#comment"During development of the central and peripheral nervous systems, neurite extension mediated via glial-cell-line-derived neurotrophic factor (GDNF) and its receptor RET is critical for neuronal differentiation. In the present study, we investigated the role of the RET substrate Dok-4 in neurite outgrowth induced by the GDNF/RET signaling pathway. In TGW neuroblastoma cells, which endogenously express both RET and Dok-4, depletion of Dok-4 through treatment with small interfering RNA resulted in a marked decrease in GDNF-stimulated neurite outgrowth. By contrast, exogenous expression of wild-type Dok-4 induced sustained p44/42 mitogen-activated protein kinase (ERK1/2) activation and enhanced neurite outgrowth. Expression of Dok-4 mutants in which the tyrosine residues at codons 187, 220 and 270, conserved between Dok-4, -5, and -6, were each replaced with a phenylalanine inhibited sustained ERK1/2 activation and neurite outgrowth. We also found that Dok-4 induced a significant activation of the small G protein Rap1 and that expression of a dominant active Rap1 mutant restored neurite outgrowth in Dok-4-depleted cells. By contrast, expression of a dominant negative Rap1 mutant impaired GDNF-stimulated neurite outgrowth from TGW cells. Finally, we found that neurite formation in cultured rat hippocampal neurons was enhanced by the expression of Dok-4. Together, our results suggest that Dok-4, through activation of the Rap1-ERK1/2 pathway, regulates GDNF-mediated neurite outgrowth during neuronal development."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.org/dc/terms/identifier"doi:10.1242/jcs.03043"xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Fukuda T."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Kurokawa K."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Hasegawa T."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Maeda K."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Takahashi M."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Shimono Y."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Uchida M."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Asai N."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Enomoto A."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Murakumo Y."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Kodama Y."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Ichihara M."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/author"Jijiwa M."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/name"J Cell Sci"xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/pages"3067-3077"xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/title"Dok-4 regulates GDNF-dependent neurite outgrowth through downstream activation of Rap1 and mitogen-activated protein kinase."xsd:string
http://purl.uniprot.org/citations/16820412http://purl.uniprot.org/core/volume"119"xsd:string
http://purl.uniprot.org/citations/16820412http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16820412
http://purl.uniprot.org/citations/16820412http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/16820412
http://purl.uniprot.org/uniprot/#_A1QJE5-mappedCitation-16820412http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16820412
http://purl.uniprot.org/uniprot/#_A8KAH9-mappedCitation-16820412http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16820412