BCR
Breakpoint cluster region protein (BCR) is best known as the N-terminal partner of the BCR-ABL1 fusion oncogene that drives chronic myeloid leukemia. In normal cells BCR is a multifunctional cytoplasmic phosphoprotein with intrinsic Ser/Thr kinase activity capable of autophosphorylation and substrate phosphorylation. Its N-terminal oligomerization domain supplies the coiled-coil that constitutively dimerizes BCR-ABL1 and unleashes its tyrosine kinase activity, while downstream regions include a Rho-GAP domain acting on RAC2 and a domain structurally related to acyltransferase-type phosphatases, letting BCR negatively regulate small-GTPase signaling. Beyond leukemia, BCR modulates the oxidative burst, vesicular trafficking, and Wnt-pathway output. Recombinant BCR fragments are used both in kinase and GAP assays and in studies of ABL-inhibitor resistance mechanisms.
