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

Datta, SR Katsov, A Hu, L Petros, A Fesik, SW Yaffe, MB Greenberg, ME

Sr. Datta et al., 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation, MOL CELL, 6(1), 2000, pp. 41-51

30

INGLESE

Article

Cell & Developmental Biology

MOLECULAR CELL

1097-2765 → ACNP

6

1

2000

41 - 51

ISI

1097-2765(200007)6:1<41:1PASKC>2.0.ZU;2-7

The Bcl-2 homology 3 (BH3) domain of prodeath Bcl-2 family members mediates their interaction with prosurvival Bcl-2 family members and promotes apopt osis, We report that survival factors trigger the phosphorylation of the pr oapoptotic Bcl-2 family member BAD at a site (Ser-155) within the BAD BH3 d omain. When BAD is bound to prosurvival Bcl-2 family members, BAD Ser-155 p hosphorylation requires the prior phosphorylation of Ser-136, which recruit s 14-3-3 proteins that then function to increase the accessibility of Ser-1 55 to survival-promoting kinases, Ser-155 phosphorylation disrupts the bind ing 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.