Pro-apototic Bcl-2 family members promote cell death by neutralizing their anti-apoptotic relatives, which otherwise maintain cell viability by regulating caspase activity. Bim belongs to the BH3-only subgroup of Bcl-2 related proteins, and exists in three distinct isoforms, BimS (short), BimL (long) and BimEL (extra long). ERK1/2 phosphorylates BimEL, resulting in rapid degradation of the isoform via the proteasome pathway. At least three sites for ERK1/2 phosphorylation exist on BimEL, whereas ERK1/2 does not effect BimS and BimL, implying a unique role for BimEL in cell survival signaling.
