The dimerization property of glutathione S-transferase partially reactivates Bcr-Abl lacking the oligomerization domain.

Bcr-Abl oncoproteins are responsible for the pathogenesis of human leukemias with a reciprocal chromosome translocation t(9;22). The amino-terminal Bcr sequence has a potential to form a homotetramer (tetramer domain), and destructions of the tetramer domain cause a complete loss of biological activities in Bcr-Abl. Here we show that Bcr-Abl in which the tetramer domain is replaced with glutathione S-transferase (GST) with a dimerizing ability (GST/Bcr-Abl-(Delta1-160)) can no longer induce an interleukin-3 (IL-3) independence in Ba/F3 cells or transform mouse bone marrow cells but still retains by 30-40% the ability to transform Rat1 cells. Compared with the wild type Bcr-Abl, autophosphorylation of GST/Bcr-Abl-(Delta1-160) in vivo was reduced by more than 50%. The Grb-2 binding to GST/Bcr-Abl-(Delta1-160) was 50% reduced in Rat1 cells and undetectable in Ba/F3 cells. In Rat1 cells expressing GST/Bcr-Abl-(Delta1-160), phosphotyrosine contents of p62 and Shc were 70% decreased.