Bcr-Abl continued

Part of the reason that wildtype Abl and the Bcr-Abl fusion act so differently is the change in form that occurs. The structure of a protein relates to the function of the protein, so any minor changes could end up changing the function completely. The change expressed in the fusion is what disrupts the regulation that wildtype Abl usually provides and increases the level of signaling beyond wildtype Abl. Wildtype interacts with multiple signal adaptors, phosphatases, transcription factors and cell cycle regulators.  It is tightly regulated and has nuclear import and export signals so it is capable of interacting in the nucleus and cytoplasm. It is regulated by intramolecular interactions and phosphorylation. When Abl kinase becomes Bcr-Abl, the new N-terminus creates a binding site for other proteins, causes the loss of the CAP domain (which is important for cell regulation) and causes the localization to be purely cytoplasmic. Overall, Bcr-Abl has binding sites for cell proliferation signaling pathways that Abl doesn’t have and has a greater kinase activity.