% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Lievens:138728,
author = {Lievens, Patricia Marie-Jeanne and Kuznetsova, Tatiana and
Kochlamazashvili, Gaga and Cesca, Fabrizia and Gorinski,
Natalya and Galil, Dalia Abdel and Cherkas, Volodimir and
Ronkina, Natalia and Lafera, Juri and Gaestel, Matthias and
Ponimaskin, Evgeni and Dityatev, Alexander},
title = {{ZDHHC}3 {T}yrosine {P}hosphorylation {R}egulates {N}eural
{C}ell {A}dhesion {M}olecule {P}almitoylation.},
journal = {Molecular and cellular biology},
volume = {36},
number = {17},
issn = {0270-7306},
address = {Washington, DC},
publisher = {Soc.},
reportid = {DZNE-2020-05050},
pages = {2208-2225},
year = {2016},
abstract = {The 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.},
keywords = {Acyltransferases: genetics / Acyltransferases: metabolism /
Animals / Cells, Cultured / Fibroblast Growth Factor 2:
metabolism / Gene Expression Regulation / Lipoylation /
Membrane Proteins: genetics / Membrane Proteins: metabolism
/ Mice / Mutation / Neural Cell Adhesion Molecules:
metabolism / Neurites: metabolism / Phosphorylation /
Receptors, Fibroblast Growth Factor: metabolism / Tyrosine:
genetics / Tyrosine: metabolism / src-Family Kinases:
metabolism / GODZ protein, mouse (NLM Chemicals) / Membrane
Proteins (NLM Chemicals) / Neural Cell Adhesion Molecules
(NLM Chemicals) / Receptors, Fibroblast Growth Factor (NLM
Chemicals) / Fibroblast Growth Factor 2 (NLM Chemicals) /
Tyrosine (NLM Chemicals) / Acyltransferases (NLM Chemicals)
/ src-Family Kinases (NLM Chemicals)},
cin = {AG Dityatev},
ddc = {570},
cid = {I:(DE-2719)1310007},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27247265},
pmc = {pmc:PMC4985929},
doi = {10.1128/MCB.00144-16},
url = {https://pub.dzne.de/record/138728},
}