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.