@article{ac8521dacc0642e9adb2fe364c74614c,
title = "Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis",
abstract = "Growth factor suppression of apoptosis correlates with the phosphorylation and inactivation of multiple proapoptotic proteins, including the BCL-2 family member BAD. However, the physiological events required for growth factors to block cell death are not well characterized. To assess the contribution of BAD inactivation to cell survival, we generated mice with point mutations in the BAD gene that abolish BAD phosphorylation at specific sites. We show that BAD phosphorylation protects cells from the deleterious effects of apoptotic stimuli and attenuates death pathway signaling by raising the threshold at which mitochondria release cytochrome c to induce cell death. These findings establish a function for endogenous BAD phosphorylation, and elucidate a mechanism by which survival kinases block apoptosis in vivo.",
author = "Datta, {Sandeep Robert} and Ranger, {Ann M.} and Lin, {Michael Z.} and Sturgill, {James Fitzhugh} and Ma, {Yong Chao} and Cowan, {Chris W.} and Pieter Dikkes and Korsmeyer, {Stanley J.} and Greenberg, {Michael E.}",
note = "Funding Information: This work was supported by National Institutes of Health PO1 grant HD 24926 (M.E.G.) and the Mental Retardation Research Center grant NIHP30-HD18655. S.J.K. was supported in part by NIH award R37CA50239. S.R.D. was supported by a Medical Scientist Training Program grant, and M.Z.L. was supported by a National Defense Science and Engineering Graduate fellowship. M.E.G. acknowledges the generous support of the F.M. Kirby Foundation to the Division of Neuroscience. A.M.R. is the Edmond J. Safra Irvington Institute Fellow. The authors would like to thank the gene targeting facility of the Children's Hospital MRRC, including Tam Thompson, Yiping Zhao, and Hong Ye for their assistance with generation of the BAD knockin mice. We thank Susan Dymecki and Frank Farley for generously providing FlpE transgenic mice, and Emer Clarke for assistance with the pre-B colony assay. The authors would also like to thank Linda Hu for assistance with antibodies, and Alex Katsov, Pei Ho, Anne Brunet, Janine Zieg, and members of the Greenberg laboratory for support and critical reading of the manuscript.",
year = "2002",
month = nov,
day = "1",
doi = "10.1016/S1534-5807(02)00326-X",
language = "English (US)",
volume = "3",
pages = "631--643",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "5",
}