Abl

The Abl family comprises two non-receptor tyrosine kinases, ABL1 (c-Abl) and ABL2 (Arg), which combine SH3, SH2 and kinase domains with extensive C-terminal regions that bind F-actin and microtubules. Normal Abl proteins link growth factor and integrin cues to cytoskeletal remodeling, DNA-damage responses and apoptosis, and are held inactive by intramolecular SH3-SH2-kinase interactions. The family is notorious because the BCR-ABL1 fusion oncogene, generated by the Philadelphia chromosome, drives chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia. ABL1 fusions also occur in rare sarcomas. Abl kinases are the founding targets of targeted cancer therapy, with imatinib, dasatinib and nilotinib transforming the treatment of these diseases.