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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-12-28
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pubmed:abstractText |
Previous studies have shown that the kinase activation loop (KAL) of the oncogenic fusion protein NPM-ALK regulates its overall tyrosine phosphorylation status and tumorigenicity. Using tandem affinity purification-mass spectrometry, we assessed how the KAL of NPM-ALK regulates the phosphorylation status of its individual tyrosines. Using the lysates of GP293 cells transfected with NPM-ALK, our highly reproducible results showed evidence of phosphorylation in all 3 tyrosines in KAL and 8 tyrosines outside KAL. We created 7 KAL mutants, each of which carried a Tyr-to-Phe mutation of >or=1 of the 3 tyrosines in KAL. A complete loss of the 8 phosphotyrosines outside KAL was found in 3 KAL mutants, and their oncogenicity (assessed by cell viability, colony formation, and the ability to phosphorylate effector proteins) was abrogated. A partial loss of the 8 phosphotyrosines was found in 4 KAL mutants, but their oncogenicity did not show simple correlation with the number of residual phosphotyrosines. Tyr-to-Phe mutations of each of the 8 phosphotyrosines outside KAL did not result in a significant decrease in the oncogenicity. In conclusion, we have provided details of how the KAL in NPM-ALK regulates its tyrosine phosphorylation pattern. Our results challenge some of the current concepts regarding the relationship between the tyrosine phosphorylation and oncogenicity of NPM-ALK.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-10939411,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-11280786,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-12648927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-15588951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-15592455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-15938644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-16189272,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-16254137,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-16432255,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-16825495,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-16909118,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-17110082,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-17203970,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-17353907,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-17416736,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-17488663,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-17519389,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-18070884,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-18370112,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-1846000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-1847379,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-18479145,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-18509351,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-18845790,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-19131589,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-19425606,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-7997262,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-8122112,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-8633037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19887368-9819383
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1083-351X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
285
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
95-103
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pubmed:dateRevised |
2011-7-19
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pubmed:meshHeading |
pubmed-meshheading:19887368-Amino Acid Sequence,
pubmed-meshheading:19887368-Amino Acid Substitution,
pubmed-meshheading:19887368-Cell Line,
pubmed-meshheading:19887368-Cell Survival,
pubmed-meshheading:19887368-Chromatography, Affinity,
pubmed-meshheading:19887368-Chromatography, Liquid,
pubmed-meshheading:19887368-Enzyme Activation,
pubmed-meshheading:19887368-Humans,
pubmed-meshheading:19887368-Molecular Sequence Data,
pubmed-meshheading:19887368-Mutant Proteins,
pubmed-meshheading:19887368-Mutation,
pubmed-meshheading:19887368-Neoplasms,
pubmed-meshheading:19887368-Phosphorylation,
pubmed-meshheading:19887368-Phosphotyrosine,
pubmed-meshheading:19887368-Protein Structure, Secondary,
pubmed-meshheading:19887368-Protein-Tyrosine Kinases,
pubmed-meshheading:19887368-Structure-Activity Relationship,
pubmed-meshheading:19887368-Tandem Mass Spectrometry
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pubmed:year |
2010
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pubmed:articleTitle |
Functional characterization of the kinase activation loop in nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) using tandem affinity purification and liquid chromatography-mass spectrometry.
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pubmed:affiliation |
Department of Laboratory Medicine and Pathology, University of Alberta and Cross Cancer Institute, Edmonton, Alberta T6G 2Z2, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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