Abstract
The Bcr-Abl nncnprotein is the primary causative factor in Philadelphia chromosome-associated leukemias. The activated tyrosine kinase of the Ber- Abl oncoprotein is the primary driving force behind its oncogenic activity. We report here that a deleted form of Bcr [Bcr(64-413)], encompassing the Abl SH2 binding domains of Bcr, reduced the phosphotyrosine content of c-Abl and Bcr-Abl within cells and inhibited Bcr-Abl autophosphorylation activity in vitro. Similarly, a Bcr peptide phosphorylated on Ser-354 blocked the c-Abl and Bcr-Abl kinases in vitro, whereas the same peptide phosphorylated on Tyr- 360 was not inhibitory. Bcr(64413) was also resistant to tyrosine phosphorylation by either activated c-Abl or Bcr-Abl. Importantly, Bcr(64- 413) interfered with the growth of Bcr-Abl-expressing cell lines. Our findings indicate that the Abl SH2 binding domain of Bcr in the phosphoserine form inhibits the Bcr-Abl oncoprotein but that tyrosine phosphorylation of this domain of Bcr reverses its inhibitory effects on Bcr-Abl. These results raise interesting questions about a possible role of Bcr or a Bcr-related molecule in modulating the activity of the Bcr-Abl oncoprotein and c-Abl itself.
Original language | English (US) |
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Pages (from-to) | 5120-5124 |
Number of pages | 5 |
Journal | Cancer Research |
Volume | 56 |
Issue number | 22 |
State | Published - Nov 15 1996 |
ASJC Scopus subject areas
- Oncology
- Cancer Research