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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
1995-12-19
|
| pubmed:abstractText |
Src-homology region 2 (SH2) domains, by binding to tyrosine-phosphorylated sequences, mediate specific protein-protein interactions important in diverse signal transduction pathways. Previous studies have shown that activated forms of the Abl tyrosine kinase, including P210BCR/ABL of human chronic myelogenous leukemia, require the SH2 domain for the transformation of fibroblasts. To determine whether SH2 is also required for Bcr/Abl to transform hematopoietic cells, we have studied two SH2 domain mutations in P210BCR/ABL: a point mutation in the conserved FLVRES motif (P210/R1033K), which interferes with phosphotyrosine-binding by SH2, and a complete deletion of SH2 (P210/delta SH2). Despite a negative effect on intrinsic Abl kinase activity, both P210 SH2 mutants were still able to transform the hematopoietic factor-dependent cell lines Ba/F3 and FDC-P1 to growth factor independence. Unexpectedly, both mutants showed greater transforming activity than wild-type P210 in a quantitative transformation assay, probably as a consequence of increased stability of the SH2 mutant proteins in vivo. Cells transformed by both P210 SH2 mutants were leukemogenic in synaptic mice and P210/r1053K mice exhibited a distinct disease phenotype, reminiscent of that induced by v-Abl. These results demonstrate that while the Abl SH2 domain is essential for BCR/ABL transformation of fibroblasts, it is dispensable for the transformation of hematopoietic factor-dependent cell lines.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Conditioned,
http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl,
http://linkedlifedata.com/resource/pubmed/chemical/Hematopoietic Cell Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0006-4971
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
86
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3897-904
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:7579359-Amino Acid Sequence,
pubmed-meshheading:7579359-Animals,
pubmed-meshheading:7579359-Cell Transformation, Neoplastic,
pubmed-meshheading:7579359-Culture Media, Conditioned,
pubmed-meshheading:7579359-Fusion Proteins, bcr-abl,
pubmed-meshheading:7579359-Hematopoietic Cell Growth Factors,
pubmed-meshheading:7579359-Hematopoietic Stem Cells,
pubmed-meshheading:7579359-Humans,
pubmed-meshheading:7579359-Mice,
pubmed-meshheading:7579359-Mice, Inbred BALB C,
pubmed-meshheading:7579359-Mice, Nude,
pubmed-meshheading:7579359-Molecular Sequence Data,
pubmed-meshheading:7579359-Mutagenesis, Site-Directed,
pubmed-meshheading:7579359-Phenotype,
pubmed-meshheading:7579359-Phosphorylation,
pubmed-meshheading:7579359-Point Mutation,
pubmed-meshheading:7579359-Protein Processing, Post-Translational,
pubmed-meshheading:7579359-Recombinant Fusion Proteins,
pubmed-meshheading:7579359-Structure-Activity Relationship,
pubmed-meshheading:7579359-Transfection,
pubmed-meshheading:7579359-src Homology Domains
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
The SH2 domain of P210BCR/ABL is not required for the transformation of hematopoietic factor-dependent cells.
|
| pubmed:affiliation |
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|