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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
37
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pubmed:dateCreated |
1995-10-12
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pubmed:abstractText |
The deregulated tyrosine kinase activity of the Bcr/Abl protein has been causally linked to the development of Philadelphia (Ph) chromosome-positive leukemia in mice and man. Abnormally tyrosine-phosphorylated substrates of the Bcr/Abl kinase in Ph-positive cells are likely to contribute to leukemogenesis by interfering with normal signal transduction pathways. We have previously shown that the adaptor molecule Crkl is a major in vivo substrate for the Bcr/Abl tyrosine kinase, and it is thought to connect Bcr/Abl with downstream effectors. In the current study, a tyrosine-phosphorylated protein with a molecular mass of approximately 120 kDa was identified which binds only to the Crkl Src homology 2 (SH2) domain in cells, including Ph-positive patient material, containing an active Bcr/Abl protein. We demonstrate here that this protein is Cbl, originally discovered as an oncogene which induces B-cell and myeloid leukemias in mice. The Crkl SH2 domain binds specifically to Cbl. The Src homology 3 (SH3) domains of Crkl do not bind to Cbl, but do bind Bcr/Abl. These findings suggest the existence of a trimolecular complex involving Bcr/Abl, Crkl, and Cbl and are consistent with a model in which Crkl mediates the oncogenic signal of Bcr/Abl to Cbl.
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/CRKL protein,
http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein v-cbl,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Retroviridae Proteins, Oncogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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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 |
15
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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 |
21468-71
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:7545163-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:7545163-Animals,
pubmed-meshheading:7545163-Binding Sites,
pubmed-meshheading:7545163-Cell Line,
pubmed-meshheading:7545163-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:7545163-Fusion Proteins, bcr-abl,
pubmed-meshheading:7545163-Glutathione Transferase,
pubmed-meshheading:7545163-Humans,
pubmed-meshheading:7545163-Leukemia, Erythroblastic, Acute,
pubmed-meshheading:7545163-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:7545163-Mice,
pubmed-meshheading:7545163-Molecular Weight,
pubmed-meshheading:7545163-Nuclear Proteins,
pubmed-meshheading:7545163-Oncogene Protein v-cbl,
pubmed-meshheading:7545163-Phosphorylation,
pubmed-meshheading:7545163-Phosphotyrosine,
pubmed-meshheading:7545163-Recombinant Fusion Proteins,
pubmed-meshheading:7545163-Retroviridae Proteins, Oncogenic,
pubmed-meshheading:7545163-Tumor Cells, Cultured,
pubmed-meshheading:7545163-Tyrosine
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pubmed:year |
1995
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pubmed:articleTitle |
Crkl is complexed with tyrosine-phosphorylated Cbl in Ph-positive leukemia.
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pubmed:affiliation |
Department of Pathology, Childrens Hospital of Los Angeles, California 90027, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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