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Science 15 April 1994:
Vol. 264. no. 5157, pp. 424 - 426
DOI: 10.1126/science.8153630
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Articles

Science, Vol 264, Issue 5157, 424-426
Copyright © 1994 by American Association for the Advancement of Science

articles

Differential complementation of Bcr-Abl point mutants with c-Myc

DE Afar, A Goga, J McLaughlin, ON Witte, and CL Sawyers

Department of Microbiology and Molecular Genetics, University of California-Los Angeles 90024-1489.

A complementation strategy was developed to define the signaling pathways activated by the Bcr-Abl tyrosine kinase. Transformation inactive point mutants of Bcr-Abl were tested for complementation with c-Myc. Single point mutations in the Src-homology 2 (SH2) domain, the major tyrosine autophosphorylation site of the kinase domain, and the Grb-2 binding site in the Bcr region impaired the transformation of fibroblasts by Bcr-Abl. Hyperexpression of c-Myc efficiently restored transformation activity only to the Bcr-Abl SH2 mutant. These data support a model in which Bcr-Abl activates at least two independent pathways for transformation. This strategy may be useful for discerning signaling pathways activated by other oncogenes.


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