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 journalArticle

527 Scopus citations

Abstract

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
Volume3
Issue number4
DOIs
StatePublished - Apr 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Harada, H., Becknell, B., Wilm, M., Mann, M., Huang, L. J. S., Taylor, S. S., Scott, J. D., & Korsmeyer, S. J. (1999). Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A. Molecular cell, 3(4), 413-422. https://doi.org/10.1016/S1097-2765(00)80469-4