CRKL binding to BCR-ABL and BCR-ABL transformation.
The SH2-SH3 domain-containing adaptor protein CRKL is the predominant tyrosine phosphorylated protein in chronic myelogenous leukemia (CML) neutrophils and BCR-ABL-expressing cell lines. The amino terminal CRKL SH3 domain binds directly to a proline-rich region in the C-terminus of BCR-ABL. BCR-ABL mutants with deletions of this region were constructed to assess ... biologic effects of eliminating the CRKL binding site. Yeast two-hybrid analysis and gel overlay assays show eradication of the direct interaction of CRKL with BCR-ABL in the proline deletion mutants. However, these BCR-ABL mutants transform myeloid cells to growth factor independence, and in these cells CRKL is tyrosine phosphorylated and associates with BCR-ABL. These findings suggest both direct and indirect interactions of CRKL with BCR-ABL. Thus, disruption of the direct interaction with BCR-ABL has not excluded a role for CRKL in BCR-ABL-mediated transformation.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Binding Sites, Cell Transformation, Neoplastic, Cells, Cultured, Fusion Proteins, bcr-abl, Humans, K562 Cells, Mutagenesis, Site-Directed, Nuclear Proteins, Phosphorylation, Proline, Protein Binding, Sequence Deletion, Transfection, Tyrosine
Adaptor Proteins, Signal Transducing, Binding Sites, Cell Transformation, Neoplastic, Cells, Cultured, Fusion Proteins, bcr-abl, Humans, K562 Cells, Mutagenesis, Site-Directed, Nuclear Proteins, Phosphorylation, Proline, Protein Binding, Sequence Deletion, Transfection, Tyrosine
Leuk. Lymphoma
Date: Mar. 01, 1999
PubMed ID: 10194128
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