14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation

被引：554

作者：

Datta, SR

Katsov, A

Hu, L

Petros, A

Fesik, SW

Yaffe, MB

Greenberg, ME

机构：

[1] Childrens Hosp, Div Neurosci, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA

[3] Abbott Labs, Nucl Magnet Resonance Res, Abbott Pk, IL 60064 USA

[4] Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduction, Boston, MA 02215 USA

[5] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA

来源：

MOLECULAR CELL | 2000年 / 6卷 / 01期

关键词：

D O I：

10.1016/S1097-2765(00)00006-X

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The Bcl-2 homology 3 (BH3) domain of prodeath Bcl-2 family members mediates their interaction with prosurvival Bcl-2 family members and promotes apoptosis, We report that survival factors trigger the phosphorylation of the proapoptotic Bcl-2 family member BAD at a site (Ser-155) within the BAD BH3 domain. When BAD is bound to prosurvival Bcl-2 family members, BAD Ser-155 phosphorylation requires the prior phosphorylation of Ser-136, which recruits 14-3-3 proteins that then function to increase the accessibility of Ser-155 to survival-promoting kinases, Ser-155 phosphorylation disrupts the binding of BAD to prosurvival Bcl-2 proteins and thereby promotes cell survival. These findings define a mechanism by which survival signals inactivate a proapoptotic Bcl-2 family member, and suggest a role for 14-3-3 proteins as cofactors that regulate sequential protein phosphorylation events.

引用

页码：41 / 51

页数：11

共 30 条

[11] Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis [J].