BCL-2 alpha encodes a novel small molecular weight GTP binding protein

Despite little sequence homology other than the GDP/GTP binding region, bcl-2 and ras proteins behave in similar fashion in many physiological and biochemical aspects. Both of them are toxin insensitive, small Mr G-proteins attached to the inner surface of the cell membrane with autophosphorylation activity and can cooperate with c-myc in cell transformation. In the case of bcl-2, however, the mechanism of activation is still unclear. One possibility is that, following antigen or mitogen stimulation, the bcl-2 protein is activated by nucleotide exchange; then the activated bcl-2 protein may interact with some other protein in the signal transduction pathway leading to cell proliferation. Dissection of the role of bcl-2 in the regulation of B-cell proliferation will be an important step in understanding its role in the pathogenesis of B-cell neoplasia.