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AF6 (ALL-1 Fusion partner in chromosome 6) was discovered as the fusion partner of ALL-1. These genes undergo translocation and fusion in acute myeloid leukemias. AF6, or p180, was also identified as a Ras-interacting protein isolated from bovine brain. AF6 binds to the GTP-Ras but not to the inactive GDP, or ineffective forms of Ras. The interaction between AF6 and Ras may regulate the Ras signaling pathway since this association was prevented by the binding of c-Raf-1 to Ras. The Ras-binding site is located within amino acids 36-206 of AF6. AF6 is 1612 amino acids in length with homology to the DLG family of proteins located in cell-cell junctions, suggesting AF6 might be important in cell-to-cell communicative events. Furthermore, AF6 has the GLGF motif characteristic of DLG proteins that include Drosophilia's Canoe, implicated in the developmental pathway triggered by Notch activation. Like AF6, Canoe was also identified as a Ras-binding protein. The amino acid sequence and biochemical property similarities between Canoe and AF6 indicate that the latter may be important in developmental processes regulated by Ras.Immunofluorescence, Immunoprecipitation, Western Blotting
