Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis

Sandeep Robert Datta, Ann M. Ranger, Michael Z. Lin, James Fitzhugh Sturgill, Yong Chao Ma, Chris W. Cowan, Pieter Dikkes, Stanley J. Korsmeyer*, Michael E. Greenberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

249 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)631-643
Number of pages13
JournalDevelopmental Cell
Volume3
Issue number5
DOIs
StatePublished - Nov 1 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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