Alternative splicing, phosphorylation and stability of Bim in vivo
Three major isoforms of Bim mRNA (EL, L and S) are detected in mouse and human cells. Whereas the corresponding proteins can be detected in human lymphocytes, BimS protein is often not detected in mouse cells. To establish the role of each isoform in vivo, we are generating mice that can produce only one Bim isoform.
Bim is also regulated by phosphorylation which promotes its ubiquitination and proteasomal degradation, but whether this is a general regulatory mechanism or holds only in certain cell types or with particular cell stimuli remains unclear. To explore the physiological role of this process of Bim regulation, we have created mice expressing a Bim mutant that cannot be ubiquitinated or cannot be phosphorylated by ERK1/2.