Source:http://linkedlifedata.com/resource/pubmed/id/15286081
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
40
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| pubmed:dateCreated |
2004-9-27
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| pubmed:databankReference | |
| pubmed:abstractText |
Activation of Ret, the receptor-tyrosine kinase for the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs), results in the recruitment and assembly of adaptor protein complexes that function to transduce signals downstream of the receptor. Here we identify Dok-6, a novel member of the Dok-4/5 subclass of the p62 Dok family of intracellular adaptor molecules, and characterize its interaction with Ret. Expression analysis reveals that Dok-6 is highly expressed in the developing central nervous system and is co-expressed with Ret in several locations, including sympathetic, sensory, and parasympathetic ganglia, as well as in the ureteric buds of the developing kidneys. Pull-down assays using the Dok-6 phosphotyrosine binding (PTB) domain and GDNF-activated Ret indicate that Dok-6 binds to the phosphorylated Ret Tyr(1062) residue. Moreover, ligand activation of Ret resulted in phosphorylation of tyrosine residue(s) located within the unique C terminus of Dok-6 predominantly through a Src-dependent mechanism, indicating that Dok-6 is a substrate of the Ret-Src signaling pathway. Interestingly, expression of Dok-6 potentiated GDNF-induced neurite outgrowth in GDNF family receptor alpha1 (GFRalpha1)-expressing Neuro2A cells that was dependent upon the C-terminal residues of Dok-6. Taken together, these data identify Dok-6 as a novel Dok-4/5-related adaptor molecule that may function in vivo to transduce signals that regulate Ret-mediated processes such as axonal projection.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Vesicular...,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-ret,
http://linkedlifedata.com/resource/pubmed/chemical/RET protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
279
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
42072-81
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:15286081-Adaptor Proteins, Vesicular Transport,
pubmed-meshheading:15286081-Animals,
pubmed-meshheading:15286081-Base Sequence,
pubmed-meshheading:15286081-Binding Sites,
pubmed-meshheading:15286081-Cell Line, Tumor,
pubmed-meshheading:15286081-Embryo, Mammalian,
pubmed-meshheading:15286081-Humans,
pubmed-meshheading:15286081-Mice,
pubmed-meshheading:15286081-Molecular Sequence Data,
pubmed-meshheading:15286081-Neurites,
pubmed-meshheading:15286081-Oncogene Proteins,
pubmed-meshheading:15286081-Protein Binding,
pubmed-meshheading:15286081-Proto-Oncogene Proteins c-ret,
pubmed-meshheading:15286081-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:15286081-Sequence Alignment,
pubmed-meshheading:15286081-Signal Transduction,
pubmed-meshheading:15286081-Tissue Distribution,
pubmed-meshheading:15286081-Transfection
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| pubmed:year |
2004
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| pubmed:articleTitle |
Dok-6, a Novel p62 Dok family member, promotes Ret-mediated neurite outgrowth.
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| pubmed:affiliation |
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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