BCR-ABL INDUCES NEURITE-LIKE STRUCTURES AND BCR LACKING THE SH2-BINDING DOMAIN INDUCES CELL ROUNDING IN PC12 CELLS

The activated tyrosine kinase oncoprotein ECR-ABL is responsible for p athogenesis of Philadelphia chromosome-positive human leukemias. Becau se BCR carries a GAP (GTPase-activating protein) activity toward cytos keleton-related small GTP-binding proteins, we utilized a neuronal PC1 2 cell system to test morphogenic potentials of BCR-ABL or ECR. We rep ort here unique morphological phenotypes of PC12 cells expressing eith er BCR-ABL or a BCR mutant which lacks the SH2-binding domain (BCR Del ta 162-413). Although MAP kinase was not activated in PC12 cells expre ssing BCR-ABL, they showed incomplete neurite extensions even in the a bsence of the nerve growth factor (NGF). Over-production of BCR Delta 162-413 in PC12 cells, on the other hand, induced cell rounding in the absence of NGF. Interestingly, those cells could hardly make terminal differentiation in the presence of NGF and continued to grow without changing their round shape, although NGF receptor as well as MAP kinas e appeared to be activated. Interestingly, the botulinum C3 toxin indu ced neurite-like structures in PC12 cells overexpressing BCR Delta 162 -413 without NGF. (C) 1996 Academic Press, Inc.