| First Author | Masters SC | Year | 2001 |
| Journal | Mol Pharmacol | Volume | 60 |
| Issue | 6 | Pages | 1325-31 |
| PubMed ID | 11723239 | Mgi Jnum | J:200329 |
| Mgi Id | MGI:5508288 | Doi | 10.1124/mol.60.6.1325 |
| Citation | Masters SC, et al. (2001) 14-3-3 inhibits Bad-induced cell death through interaction with serine-136. Mol Pharmacol 60(6):1325-31 |
| abstractText | 14-3-3 proteins are a family of multifunctional phosphoserine binding molecules that can serve as effectors of survival signaling. Understanding the molecular basis for the prosurvival effect of 14-3-3 may lead to the development of agents useful in the treatment of disorders involving dysregulated apoptosis. One target of 14-3-3 is the proapoptotic Bcl-2 family member Bad. Serine phosphorylation of Bad is associated with 14-3-3 binding and inhibition of Bad-induced cell death, but the relative contributions of the three known phosphorylation sites to 14-3-3 binding have not been established. Here we demonstrate that S136 of Bad is vital for 14-3-3 interaction, but S112 seems to be dispensable. 14-3-3/Bad interaction was strictly dependent on the presence of phosphorylated S136 in vitro, in yeast, and in mammalian cells. However, mutation of S112 did not affect 14-3-3 binding. The death caused by wild-type and S112A Bad, but not that caused by S136A Bad, could be almost completely abrogated by 14-3-3. These data support a critical role for 14-3-3 in regulating Bad proapoptotic activity. The effect of 14-3-3 on Bad is controlled largely by phosphorylation of S136, whereas S112 may represent a 14-3-3-independent pathway. |
