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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2001-3-13
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pubmed:abstractText |
Beta-catenin undergoes both serine and tyrosine phosphorylation. Serine phosphorylation in the amino terminus targets beta-catenin for proteasome degradation, whereas tyrosine phosphorylation in the COOH terminus influences interaction with E-cadherin. We examined the tyrosine phosphorylation status of beta-catenin in melanoma cells expressing proteasome-resistant beta-catenin, as well as the effects that perturbation of beta-catenin tyrosine phosphorylation had on its association with E-cadherin and on its transcriptional activity. Beta-catenin is tyrosine phosphorylated in three melanoma cell lines and associates with both the ErbB2 receptor tyrosine kinase and the LAR receptor tyrosine phosphatase. Geldanamycin, a drug which destabilizes ErbB2, caused rapid cellular depletion of the kinase and loss of its association with beta-catenin without perturbing either LAR or beta-catenin levels or LAR/beta-catenin association. Geldanamycin also stimulated tyrosine dephosphorylation of beta-catenin and increased beta-catenin/E-cadherin association, resulting in substantially decreased cell motility. Geldanamycin also decreased the nuclear beta-catenin level and inhibited beta-catenin-driven transcription, as assessed using two different beta-catenin-sensitive reporters and the endogenous cyclin D1 gene. These findings were confirmed by transient transfection of two beta-catenin point mutants, Tyr-654Phe and Tyr-654Glu, which, respectively, mimic the dephosphorylated and phosphorylated states of Tyr-654, a tyrosine residue contained within the beta-catenin-ErbB2-binding domain. These data demonstrate that the functional activity of proteasome-resistant beta-catenin is regulated further by geldanamycin-sensitive tyrosine phosphorylation in melanoma cells.
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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/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PTPRA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTPRF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Quinones,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor-Like Protein Tyrosine...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor-Like Protein Tyrosine...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/geldanamycin
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
61
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1671-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11245482-Antibiotics, Antineoplastic,
pubmed-meshheading:11245482-Benzoquinones,
pubmed-meshheading:11245482-Cadherins,
pubmed-meshheading:11245482-Cell Movement,
pubmed-meshheading:11245482-Cysteine Endopeptidases,
pubmed-meshheading:11245482-Cysteine Proteinase Inhibitors,
pubmed-meshheading:11245482-Cytoskeletal Proteins,
pubmed-meshheading:11245482-Humans,
pubmed-meshheading:11245482-Lactams, Macrocyclic,
pubmed-meshheading:11245482-Melanoma,
pubmed-meshheading:11245482-Multienzyme Complexes,
pubmed-meshheading:11245482-Nerve Tissue Proteins,
pubmed-meshheading:11245482-Phosphorylation,
pubmed-meshheading:11245482-Point Mutation,
pubmed-meshheading:11245482-Proteasome Endopeptidase Complex,
pubmed-meshheading:11245482-Protein Tyrosine Phosphatases,
pubmed-meshheading:11245482-Quinones,
pubmed-meshheading:11245482-Receptor, erbB-2,
pubmed-meshheading:11245482-Receptor-Like Protein Tyrosine Phosphatases, Class 2,
pubmed-meshheading:11245482-Receptor-Like Protein Tyrosine Phosphatases, Class 4,
pubmed-meshheading:11245482-Receptors, Cell Surface,
pubmed-meshheading:11245482-Trans-Activators,
pubmed-meshheading:11245482-Transcription, Genetic,
pubmed-meshheading:11245482-Transcriptional Activation,
pubmed-meshheading:11245482-Transfection,
pubmed-meshheading:11245482-Tumor Cells, Cultured,
pubmed-meshheading:11245482-Tyrosine,
pubmed-meshheading:11245482-beta Catenin
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pubmed:year |
2001
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pubmed:articleTitle |
Geldanamycin abrogates ErbB2 association with proteasome-resistant beta-catenin in melanoma cells, increases beta-catenin-E-cadherin association, and decreases beta-catenin-sensitive transcription.
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pubmed:affiliation |
Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, Rockville, Maryland 20850, USA.
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pubmed:publicationType |
Journal Article
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