BCR/ABL can activate ERKs via Ras and Rap1. BCR/ABL is a fusion protein between the BCR and the kinase ABL. The ABL kinase contains Src homology domains 1, 2, and 3 (SH1, SH2, and SH3) and a proline-rich domain (PRD). BCR/ABL binds multiple proteins to trigger intracellular signaling cascades. The binding of Grb2, Cbl, and CrkL are shown here. Grb2 associates with BCR/ABL as a complex with the RasGEF SOS (son of sevenless). The SH2 domain of Grb2 binds to phosphotyrosine 177 in the BCR region of BCR-ABL to allow SOS to activate Ras (Ras-GTP), which in turn recruits Raf-1 (and possibly B-Raf) to activate ERK. CrkL exists as a complex with the Rap1 GEF C3G. Recruitment of CrkL/C3G to the PRD of BCR/ABL (via a CrkL SH3 domain) allows C3G to activate Rap1 (Rap1-GTP), which recruits B-Raf to activate ERK. The scaffold molecule Cbl binds the SH2 domain of BCR/ABL and may also participate in the complex with CrkL/C3G.