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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
24
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pubmed:dateCreated |
1995-12-28
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pubmed:abstractText |
Growth factor-binding protein 2 (Grb2) is an adaptor protein that links tyrosine kinases to Ras. BCR-ABL is a tyrosine kinase oncoprotein that is implicated in the pathogenesis of Philadelphia chromosome (Ph1)-positive leukemias. Grb2 forms a complex with BCR-ABL and the nucleotide exchange factor Sos that leads to the activation of the Ras protooncogene. In this report we demonstrate that Grb2 mutant proteins lacking amino- or carboxyl-terminal src homology SH3 domains suppress BCR-ABL-induced Ras activation and reverse the oncogenic phenotype. The Grb2 SH3-deletion mutant proteins bind to BCR-ABL and do not impair tyrosine kinase activity. Expression of the Grb2 SH3-deletion mutant proteins in BCR-ABL-transformed Rat-1 fibroblasts and in the human Ph1-positive leukemic cell line K562 inhibits their ability to grow as foci in soft agar and form tumors in nude mice. Furthermore, expression of the Grb2 SH3-deletion mutants in K562 cells induced their differentiation. Because Ras plays an important role in signaling by receptor and nonreceptor tyrosine kinases, the use of interfering mutant Grb2 proteins may be applied to block the proliferation of other cancers that depend in part on activated tyrosine kinases for growth.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-1313769,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-1322798,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-1372395,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-1461284,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-14731533,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-1501893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-15335710,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-163658,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-1643657,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-1643658,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-1656993,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-2005881,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-2302733,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-2501665,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-2725497,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-2852893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-3090687,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-3145408,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-6204766,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-7505115,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-7512734,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-7521298,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-7565705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-7691239,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-7807010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-7813429,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-7862122,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8013457,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8112292,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8153630,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8178156,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8188688,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8195176,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8206897,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8236435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8334704,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8335690,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8402896,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8431353,
http://linkedlifedata.com/resource/pubmed/commentcorrection/7479904-8483497
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Grb2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Grb2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/HRAS protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-raf,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins p21(ras)
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
92
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10889-93
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:7479904-Humans,
pubmed-meshheading:7479904-Animals,
pubmed-meshheading:7479904-Mice,
pubmed-meshheading:7479904-Proteins,
pubmed-meshheading:7479904-Rats,
pubmed-meshheading:7479904-Cell Transformation, Neoplastic,
pubmed-meshheading:7479904-Cell Division,
pubmed-meshheading:7479904-Tumor Cells, Cultured,
pubmed-meshheading:7479904-Cell Differentiation,
pubmed-meshheading:7479904-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:7479904-Structure-Activity Relationship,
pubmed-meshheading:7479904-Mice, Nude,
pubmed-meshheading:7479904-Signal Transduction,
pubmed-meshheading:7479904-Protein-Serine-Threonine Kinases,
pubmed-meshheading:7479904-Protein-Tyrosine Kinases,
pubmed-meshheading:7479904-Proto-Oncogene Proteins p21(ras),
pubmed-meshheading:7479904-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:7479904-Proto-Oncogene Proteins,
pubmed-meshheading:7479904-Fusion Proteins, bcr-abl,
pubmed-meshheading:7479904-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:7479904-GRB2 Adaptor Protein
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