PMID- 10230394 OWN - NLM STAT- MEDLINE DCOM- 19990527 LR - 20190915 IS - 1097-2765 (Print) IS - 1097-2765 (Linking) VI - 3 IP - 4 DP - 1999 Apr TI - Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A. PG - 413-22 AB - 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. FAU - Harada, H AU - Harada H AD - Division of Molecular Oncology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA. FAU - Becknell, B AU - Becknell B FAU - Wilm, M AU - Wilm M FAU - Mann, M AU - Mann M FAU - Huang, L J AU - Huang LJ FAU - Taylor, S S AU - Taylor SS FAU - Scott, J D AU - Scott JD FAU - Korsmeyer, S J AU - Korsmeyer SJ LA - eng GR - 5R01 CA 50239-10/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell JT - Molecular cell JID - 9802571 RN - 0 (Carrier Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (Interleukin-3) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (bcl-Associated Death Protein) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinase Type II) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) SB - IM MH - Animals MH - Apoptosis MH - Carrier Proteins/*metabolism MH - Cyclic AMP-Dependent Protein Kinase Type II MH - Cyclic AMP-Dependent Protein Kinases/*metabolism MH - Enzyme Activation MH - Enzyme Inhibitors/pharmacology MH - Interleukin-3/pharmacology MH - Mitochondria/*enzymology MH - Phosphorylation MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Signal Transduction MH - Tumor Cells, Cultured MH - bcl-Associated Death Protein EDAT- 1999/05/07 00:00 MHDA- 1999/05/07 00:01 CRDT- 1999/05/07 00:00 PHST- 1999/05/07 00:00 [pubmed] PHST- 1999/05/07 00:01 [medline] PHST- 1999/05/07 00:00 [entrez] AID - S1097-2765(00)80469-4 [pii] AID - 10.1016/s1097-2765(00)80469-4 [doi] PST - ppublish SO - Mol Cell. 1999 Apr;3(4):413-22. doi: 10.1016/s1097-2765(00)80469-4.