Abstract
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.
Original language | English (US) |
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Pages (from-to) | 119-126 |
Number of pages | 8 |
Journal | Leukemia and Lymphoma |
Volume | 33 |
Issue number | 1-2 |
DOIs | |
State | Published - Jan 1 1999 |
Keywords
- BCR-ABL
- CRKL
- Src homology domains
- Tyrosine phosphorylation
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research