Bcl-2 overexpression disrupts the morphology of PC12 cells through reduced ERK activation.
Bcl-2 has been hypothesized to regulate many cellular functions in addition to its well-characterized role in the prevention of programmed cell death. To understand the role of Bcl-2 in regulating cell morphology and to explore the mechanism of this effect, we examined the effects of Bcl-2 overexpression on the morphology of PC12 cells in culture. We demonstrate that the overexpression of Bcl-2 in PC12 cells results in altered cell morphology and reduced actin expression. Analysis of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation reveals that the morphological changes seen after bcl-2 transfection are associated with reduced ERK activation. Treatment of control (mock-transfected) PC12 cells with the mitogen-activated ERK-activating kinase (MEK) inhibitor PD98059 converts their flat, process-bearing morphology into the rounded, process-free morphology of bcl-2-transfected cells, further confirming the association of ERK activation with altered cell shape. In conclusion, the present study describes a novel function of Bcl-2 in regulating cell shape through reduced ERK activation.
Mi
Zhiping
Z
Pediatric Center for Neuroscience, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15213, USA.
Mirnics
Zeljka Korade
ZK
Schor
Nina Felice
NF
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology*; D016716:PC12 Cells / Q000166:cytology* / Q000378:metabolism*; D010590:Phalloidine; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D051381:Rats; D013997:Time Factors
D000199:Actins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D019253:Proto-Oncogene Proteins c-bcl-2; D010590:Phalloidine; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one