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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2000-8-25
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pubmed:abstractText |
Bcr-Abl contributes prominently to the development of most chronic myeloid leukemias (CMLs). Prior work has identified the adapter protein CRKL as a major substrate of the Bcr-Abl tyrosine kinase. CRKL can also bind via its first SH3 domain [SH3(1)] to specific sequences in Bcr-Abl. Cell-penetrating peptides were developed that bind with high affinity and selectivity to the SH3(1) domain of CRKL. They disrupt Bcr-Abl-CRKL complexes and strongly reduce the proliferation of primary CML blast cells and cell lines established from Bcr-Abl-positive patients. Activation-specific antibodies against phosphorylated MAP kinase (MAPK) showed that MAPK activity is down-regulated in blast cells treated with the CRKLSH3(1) blocker peptides. We conclude that the Bcr-Abl-CRKL complexes are largely dependent on the CRKLSH3(1) domain, that the central mitogenic cascade is down-regulated as a consequence of the disruption of CRKLSH3(1) interactions, and that CRKL therefore contributes to the proliferation of CML blast 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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/CRKL protein,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Calreticulin,
http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleoproteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0892-6638
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pubmed:author |
pubmed-author:AdermannKK,
pubmed-author:ArlinghausR BRB,
pubmed-author:EstrovZZ,
pubmed-author:EulitzMM,
pubmed-author:FellerS MSM,
pubmed-author:KardinalCC,
pubmed-author:KonkolBB,
pubmed-author:LipJJ,
pubmed-author:PosernGG,
pubmed-author:SchulzAA,
pubmed-author:TalpazMM
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1529-38
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10928987-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:10928987-Amino Acid Sequence,
pubmed-meshheading:10928987-Animals,
pubmed-meshheading:10928987-Binding Sites,
pubmed-meshheading:10928987-Calcium-Binding Proteins,
pubmed-meshheading:10928987-Calreticulin,
pubmed-meshheading:10928987-Cell Division,
pubmed-meshheading:10928987-Cell Membrane,
pubmed-meshheading:10928987-Cell Membrane Permeability,
pubmed-meshheading:10928987-Fluorescent Antibody Technique,
pubmed-meshheading:10928987-Fusion Proteins, bcr-abl,
pubmed-meshheading:10928987-Half-Life,
pubmed-meshheading:10928987-Humans,
pubmed-meshheading:10928987-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:10928987-Lymphocyte Activation,
pubmed-meshheading:10928987-Mitogen-Activated Protein Kinases,
pubmed-meshheading:10928987-Molecular Sequence Data,
pubmed-meshheading:10928987-Nuclear Proteins,
pubmed-meshheading:10928987-Peptides,
pubmed-meshheading:10928987-Protein Binding,
pubmed-meshheading:10928987-Rats,
pubmed-meshheading:10928987-Recombinant Fusion Proteins,
pubmed-meshheading:10928987-Ribonucleoproteins,
pubmed-meshheading:10928987-Spectrometry, Fluorescence,
pubmed-meshheading:10928987-Tumor Cells, Cultured,
pubmed-meshheading:10928987-src Homology Domains
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pubmed:year |
2000
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pubmed:articleTitle |
Cell-penetrating SH3 domain blocker peptides inhibit proliferation of primary blast cells from CML patients.
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pubmed:affiliation |
Laboratory of Molecular Oncology, MSZ, Universität Würzburg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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