BCR-ABL induces neurite-like structures and BCR lacking the SH2-binding domain induces cell rounding in PC12 cells.
The activated tyrosine kinase oncoprotein BCR-ABL is responsible for pathogenesis of Philadelphia chromosome-positive human leukemias. Because BCR carries a GAP (GTPase-activating protein) activity toward cytoskeleton-related small GTP-binding proteins, we utilized a neuronal PC12 cell system to test morphogenic potentials of BCR-ABL or BCR. We report here unique morphological phenotypes of PC12 cells expressing either BCR-ABL or a BCR mutant which lacks the SH2-binding domain (BCR Delta162-413). Although MAP kinase was not activated in PC12 cells expressing BCR-ABL, they showed incomplete neurite extensions even in the absence of the nerve growth factor (NGF). Overproduction of BCR Delta162-413 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 kinase appeared to be activated. Interestingly, the botulinum C3 toxin induced neurite-like structures in PC12 cells overexpressing BCR Delta162-413 without NGF.
Maru
Y
Y
Institute of Medical Science, University of Tokyo, Tokyo, 108, Japan.
Witte
O N
ON
Shibuya
M
M
D000818:Animals; D001905:Botulinum Toxins / Q000633:toxicity; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D048429:Cell Size; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure*; D016716:PC12 Cells; D010641:Phenotype; D051381:Rats; D017384:Sequence Deletion; D018631:ras Proteins / Q000494:pharmacology; D018909:src Homology Domains
D009414:Nerve Growth Factors; D016044:Fusion Proteins, bcr-abl; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D001905:Botulinum Toxins; D018631:ras Proteins