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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
35
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pubmed:dateCreated |
1995-10-4
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pubmed:abstractText |
Neurotrophin-3 binds to the receptor tyrosine kinase, TrkC. Several naturally occurring splice variants of TrkC exist including those with 14- and 39-amino acid inserts within the tyrosine kinase homology region. When expressed in fibroblasts, full-length TrkC, but not the kinase insert variants, mediated neurotrophin-3-stimulated cell proliferation. We investigated the molecular basis of this signaling defect. The kinase inserts blocked the ability of TrkC to mediate neurotrophin-3 stimulated c-myc and c-fos transcription and activation of the AP-1 transcriptional complex. In cells expressing full-length TrkC, neurotrophin-3 promoted a sustained activation of mitogen-activated protein kinase; TrkC containing kinase inserts only mediated transient activation of mitogen-activated protein kinase. The kinase inserts specifically blocked neurotrophin-3-stimulated autophosphorylation of the phospholipase C gamma binding site on TrkC (tyrosine 789) resulting in a severe reduction in phospholipase C gamma association with TrkC and its tyrosine phosphorylation. Neurotrophin-3-stimulated phosphorylation of the Shc binding site (tyrosine 485) on TrkC, and tyrosine phosphorylation of Shc itself, was unaffected by the kinase inserts; however, the kinase inserts blocked high affinity Shc association with TrkC. It is proposed that the lack of high affinity binding of Shc and/or phospholipase C gamma to the TrkC kinase insert variants may be responsible for the inability of these variants to bring about a full biological response in fibroblasts.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotrophin 3,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Ciliary Neurotrophic...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, trkC,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nerve Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
270
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
20384-90
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:7657612-3T3 Cells,
pubmed-meshheading:7657612-Amino Acid Sequence,
pubmed-meshheading:7657612-Animals,
pubmed-meshheading:7657612-Base Sequence,
pubmed-meshheading:7657612-Binding Sites,
pubmed-meshheading:7657612-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:7657612-Cell Division,
pubmed-meshheading:7657612-DNA Primers,
pubmed-meshheading:7657612-Enzyme Activation,
pubmed-meshheading:7657612-Fibroblasts,
pubmed-meshheading:7657612-Isoenzymes,
pubmed-meshheading:7657612-Kinetics,
pubmed-meshheading:7657612-Mice,
pubmed-meshheading:7657612-Molecular Sequence Data,
pubmed-meshheading:7657612-Mutagenesis, Insertional,
pubmed-meshheading:7657612-Nerve Growth Factors,
pubmed-meshheading:7657612-Neurotrophin 3,
pubmed-meshheading:7657612-Phosphorylation,
pubmed-meshheading:7657612-Protein-Tyrosine Kinases,
pubmed-meshheading:7657612-Receptor, Ciliary Neurotrophic Factor,
pubmed-meshheading:7657612-Receptor, trkC,
pubmed-meshheading:7657612-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:7657612-Receptors, Nerve Growth Factor,
pubmed-meshheading:7657612-Recombinant Proteins,
pubmed-meshheading:7657612-Signal Transduction,
pubmed-meshheading:7657612-Substrate Specificity,
pubmed-meshheading:7657612-Transfection,
pubmed-meshheading:7657612-Type C Phospholipases
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pubmed:year |
1995
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pubmed:articleTitle |
Naturally occurring tyrosine kinase inserts block high affinity binding of phospholipase C gamma and Shc to TrkC and neurotrophin-3 signaling.
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pubmed:affiliation |
Department of Biochemistry, School of Medical Sciences, University of Bristol, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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