Phospho-Bim (Ser69) Antibody #4581

Bim/Bod is a pro-apoptotic protein belonging to the BH3-only group of Bcl-2 family members including Bad, Bid, Bik, Hrk, and Noxa that contain a BH3 domain but lack other conserved BH1 or BH2 domains (1,2). Bim induces apoptosis by binding to and antagonizing anti-apoptotic members of the Bcl-2 family. Interactions have been observed with Bcl-2, Bcl-xL, Mcl-1, Bcl-w, Bfl-1, and BHRF-1 (1,2). Bim functions in regulating apoptosis associated with thymocyte negative selection and following growth factor withdrawal, during which Bim expression is elevated (3-6). Three major isoforms of Bim are generated by alternative splicing: Bim_EL, Bim_L, and Bim_S (1). The shortest form, Bim_S, is the most cytotoxic and is generally only transiently expressed during apoptosis. The Bim_EL and Bim_L isoforms may be sequestered to the dynein motor complex through an interaction with the dynein light chain and released from this complex during apoptosis (7). Apoptotic activity of these longer isoforms may be regulated by phosphorylation (8,9). Environmental stress triggers Bim phosphorylation by JNK and results in its dissociation from the dynein complex and increased apoptotic activity.
Erk1/2-dependent phosphorylation of Bim_EL at Ser69 (Ser65 in mouse and rat) in response to growth factor stimulation can promote its proteasome-mediated degradation and enhance cell survival (6,10,11).