ENABLED, A DOSAGE-SENSITIVE SUPPRESSOR OF MUTATIONS IN THE DROSOPHILAABL TYROSINE KINASE, ENCODES AN ABL SUBSTRATE WITH SH3 DOMAIN-BINDINGPROPERTIES

Genetic screens for dominant second-site mutations that suppress the l ethality of Abl mutations in Drosophila identified alleles of only one gene, enabled (ena). We report that the ena protein contains proline- rich motifs and binds to Abl and Src SH3 domains, ena is also a substr ate for the Abl kinase; tyrosine phosphorylation of ena is increased w hen it is coexpressed in cells with human or Drosophila Abl and endoge nous ena tyrosine phosphorylation is reduced in Abl mutant animals. Li ke Abl, ena is expressed at highest levels in the axons of the embryon ic nervous system and ena mutant embryos have defects in axonal archit ecture. We conclude that a critical function of Drosophila Abl is to p hosphorylate and negatively regulate ena protein during neural develop ment.