Bone marrow tyrosine kinase on chromosome X (BMX)

Bone marrow tyrosine kinase on chromosome X (BMX) is a non-receptor tyrosine kinase belonging to the Tec family. It is encoded by the BMX gene, located on the X chromosome, and is structured with regulatory domains typical of Tec kinases, including PH, BH, SH3, SH2, and a carboxyl-terminal kinase domain. BMX is expressed in various cell types, especially in myeloid hematopoietic lineage cells, endothelial cells, and multiple cancer types. Functionally, it regulates cellular signal transduction processes such as the response to cytokines, cell proliferation, immune response, and monocyte/macrophage trafficking. BMX activity is implicated in inflammation, oncogenesis, angiogenesis, and cardiac hypertrophy. Crystal structures have revealed key features of BMX kinase domain and have guided early drug discovery efforts. Inhibitors like dasatinib bind BMX in its ATP-binding pocket, although no clinically approved selective BMX inhibitor is currently available. Knockout and silencing experiments in model organisms indicate roles for BMX in both disease states and cell signaling, but also suggest the existence of a therapeutic window with limited toxicity under certain conditions.

Other names

BMXcytoplasmic tyrosine-protein kinase BMXbone marrow kinase in the X chromosome

ATP-competitive inhibition of the kinase domain (by molecules such as dasatinib and PP2, which bind in the ATP-binding pocket and stabilize inactive conformations) Modulation of downstream signaling via inhibition of STAT phosphorylation and other effectors