The Bcr-Abl oncoprotein is the primary causative factor in Philadelphia chromosome-associated leukemias. The activated tyrosine kinase of the Bcr-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(64–413) 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 from 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.


This work was supported by grants from the NIH (CA65611 and CA16672). R. B. A. holds the Stringer chair of Cancer Research.

This content is only available via PDF.