Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A

Hisashi Harada, Brian Becknell, Matthias Wilm, Matthias Mann, Lily Jun shen Huang, Susan S. Taylor, John D. Scott, Stanley J. Korsmeyer

Research output: Contribution to journalArticlepeer-review

559 Scopus citations


Signaling pathways between cell surface receptors and the BCL-2 family of proteins regulate cell death. Survival factors induce the phosphorylation and inactivation of BAD, a proapoptotic member. Purification of BAD kinase(s) identified membrane-based cAMP-dependent protein kinase (PKA) as a BAD Ser- 112 (S112) site-specific kinase. PKA-specific inhibitors blocked the IL-3- induced phosphorylation on S112 of endogenous BAD as well as mitochondria- based BAD S112 kinase activity. A blocking peptide that disrupts type II PKA holoenzyme association with A-kinase-anchoring proteins (AKAPs) also inhibited BAD phosphorylation and eliminated the BAD S112 kinase activity at mitochondria. Thus, the anchoring of PKA to mitochondria represents a focused subcellular kinase/substrate interaction that inactivates BAD at its target organelle in response to a survival factor.

Original languageEnglish (US)
Pages (from-to)413-422
Number of pages10
JournalMolecular cell
Issue number4
StatePublished - Apr 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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