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000138728 0247_ $$2doi$$a10.1128/MCB.00144-16
000138728 0247_ $$2pmid$$apmid:27247265
000138728 0247_ $$2pmc$$apmc:PMC4985929
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000138728 0247_ $$2ISSN$$a1067-8824
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000138728 0247_ $$2ISSN$$a1069-5524
000138728 037__ $$aDZNE-2020-05050
000138728 041__ $$aEnglish
000138728 082__ $$a570
000138728 1001_ $$0P:(DE-HGF)0$$aLievens, Patricia Marie-Jeanne$$b0
000138728 245__ $$aZDHHC3 Tyrosine Phosphorylation Regulates Neural Cell Adhesion Molecule Palmitoylation.
000138728 260__ $$aWashington, DC$$bSoc.$$c2016
000138728 264_1 $$2Crossref$$3online$$bAmerican Society for Microbiology$$c2016-05-31
000138728 264_1 $$2Crossref$$3print$$bAmerican Society for Microbiology$$c2016-09-01
000138728 3367_ $$2DRIVER$$aarticle
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000138728 3367_ $$2BibTeX$$aARTICLE
000138728 3367_ $$2ORCID$$aJOURNAL_ARTICLE
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000138728 520__ $$aThe neural cell adhesion molecule (NCAM) mediates cell-cell and cell-matrix adhesion. It is broadly expressed in the nervous system and regulates neurite outgrowth, synaptogenesis, and synaptic plasticity. Previous in vitro studies revealed that palmitoylation of NCAM is required for fibroblast growth factor 2 (FGF2)-stimulated neurite outgrowth and identified the zinc finger DHHC (Asp-His-His-Cys)-containing proteins ZDHHC3 and ZDHHC7 as specific NCAM-palmitoylating enzymes. Here, we verified that FGF2 controlled NCAM palmitoylation in vivo and investigated molecular mechanisms regulating NCAM palmitoylation by ZDHHC3. Experiments with overexpression and pharmacological inhibition of FGF receptor (FGFR) and Src revealed that these kinases control tyrosine phosphorylation of ZDHHC3 and that ZDHHC3 is phosphorylated by endogenously expressed FGFR and Src proteins. By site-directed mutagenesis, we found that Tyr18 is an FGFR1-specific ZDHHC3 phosphorylation site, while Tyr295 and Tyr297 are specifically phosphorylated by Src kinase in cell-based and cell-free assays. Abrogation of tyrosine phosphorylation increased ZDHHC3 autopalmitoylation, enhanced interaction with NCAM, and upregulated NCAM palmitoylation. Expression of ZDHHC3 with tyrosine mutated in cultured hippocampal neurons promoted neurite outgrowth. Our findings for the first time highlight that FGFR- and Src-mediated tyrosine phosphorylation of ZDHHC3 modulates ZDHHC3 enzymatic activity and plays a role in neuronal morphogenesis.
000138728 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
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000138728 650_7 $$2NLM Chemicals$$aGODZ protein, mouse
000138728 650_7 $$2NLM Chemicals$$aMembrane Proteins
000138728 650_7 $$2NLM Chemicals$$aNeural Cell Adhesion Molecules
000138728 650_7 $$2NLM Chemicals$$aReceptors, Fibroblast Growth Factor
000138728 650_7 $$0103107-01-3$$2NLM Chemicals$$aFibroblast Growth Factor 2
000138728 650_7 $$042HK56048U$$2NLM Chemicals$$aTyrosine
000138728 650_7 $$0EC 2.3.-$$2NLM Chemicals$$aAcyltransferases
000138728 650_7 $$0EC 2.7.10.2$$2NLM Chemicals$$asrc-Family Kinases
000138728 650_2 $$2MeSH$$aAcyltransferases: genetics
000138728 650_2 $$2MeSH$$aAcyltransferases: metabolism
000138728 650_2 $$2MeSH$$aAnimals
000138728 650_2 $$2MeSH$$aCells, Cultured
000138728 650_2 $$2MeSH$$aFibroblast Growth Factor 2: metabolism
000138728 650_2 $$2MeSH$$aGene Expression Regulation
000138728 650_2 $$2MeSH$$aLipoylation
000138728 650_2 $$2MeSH$$aMembrane Proteins: genetics
000138728 650_2 $$2MeSH$$aMembrane Proteins: metabolism
000138728 650_2 $$2MeSH$$aMice
000138728 650_2 $$2MeSH$$aMutation
000138728 650_2 $$2MeSH$$aNeural Cell Adhesion Molecules: metabolism
000138728 650_2 $$2MeSH$$aNeurites: metabolism
000138728 650_2 $$2MeSH$$aPhosphorylation
000138728 650_2 $$2MeSH$$aReceptors, Fibroblast Growth Factor: metabolism
000138728 650_2 $$2MeSH$$aTyrosine: genetics
000138728 650_2 $$2MeSH$$aTyrosine: metabolism
000138728 650_2 $$2MeSH$$asrc-Family Kinases: metabolism
000138728 7001_ $$0P:(DE-HGF)0$$aKuznetsova, Tatiana$$b1
000138728 7001_ $$0P:(DE-HGF)0$$aKochlamazashvili, Gaga$$b2
000138728 7001_ $$0P:(DE-HGF)0$$aCesca, Fabrizia$$b3
000138728 7001_ $$0P:(DE-HGF)0$$aGorinski, Natalya$$b4
000138728 7001_ $$0P:(DE-HGF)0$$aGalil, Dalia Abdel$$b5
000138728 7001_ $$0P:(DE-HGF)0$$aCherkas, Volodimir$$b6
000138728 7001_ $$0P:(DE-HGF)0$$aRonkina, Natalia$$b7
000138728 7001_ $$0P:(DE-HGF)0$$aLafera, Juri$$b8
000138728 7001_ $$0P:(DE-HGF)0$$aGaestel, Matthias$$b9
000138728 7001_ $$0P:(DE-HGF)0$$aPonimaskin, Evgeni$$b10$$eCorresponding author
000138728 7001_ $$0P:(DE-2719)2810577$$aDityatev, Alexander$$b11$$eLast author
000138728 77318 $$2Crossref$$3journal-article$$a10.1128/mcb.00144-16$$b : American Society for Microbiology, 2016-05-31$$n17$$p2208-2225$$tMolecular and Cellular Biology$$v36$$x0270-7306$$y2016
000138728 773__ $$0PERI:(DE-600)1474919-1$$a10.1128/MCB.00144-16$$gVol. 36, no. 17, p. 2208 - 2225$$n17$$p2208-2225$$q36:17<2208 - 2225$$tMolecular and cellular biology$$v36$$x0270-7306$$y2016
000138728 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985929
000138728 909CO $$ooai:pub.dzne.de:138728$$pVDB
000138728 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810577$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b11$$kDZNE
000138728 9131_ $$0G:(DE-HGF)POF3-342$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$aDE-HGF$$bForschungsbereich Gesundheit$$lErkrankungen des Nervensystems$$vDisease Mechanisms and Model Systems$$x0
000138728 9141_ $$y2016
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