PMID- 10195903
OWN - NLM
STAT- MEDLINE
DCOM- 19990504
LR  - 20190619
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 284
IP  - 5412
DP  - 1999 Apr 9
TI  - Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD.
PG  - 339-43
AB  - The Ca2+-activated protein phosphatase calcineurin induces apoptosis, but the
      mechanism is unknown. Calcineurin was found to dephosphorylate BAD, a
      pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization
      with Bcl-xL and promoting apoptosis. The Ca2+-induced dephosphorylation of BAD
      correlated with its dissociation from 14-3-3 in the cytosol and translocation to 
      mitochondria where Bcl-xL resides. In hippocampal neurons, L-glutamate, an
      inducer of Ca2+ influx and calcineurin activation, triggered mitochondrial
      targeting of BAD and apoptosis, which were both suppressible by coexpression of a
      dominant-inhibitory mutant of calcineurin or pharmacological inhibitors of this
      phosphatase. Thus, a Ca2+-inducible mechanism for apoptosis induction operates by
      regulating BAD phosphorylation and localization in cells.
FAU - Wang, H G
AU  - Wang HG
AD  - The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
FAU - Pathan, N
AU  - Pathan N
FAU - Ethell, I M
AU  - Ethell IM
FAU - Krajewski, S
AU  - Krajewski S
FAU - Yamaguchi, Y
AU  - Yamaguchi Y
FAU - Shibasaki, F
AU  - Shibasaki F
FAU - McKeon, F
AU  - McKeon F
FAU - Bobo, T
AU  - Bobo T
FAU - Franke, T F
AU  - Franke TF
FAU - Reed, J C
AU  - Reed JC
LA  - eng
GR  - AG-1593/AG/NIA NIH HHS/United States
GR  - CA-69381/CA/NCI NIH HHS/United States
GR  - HD25938/HD/NICHD NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (14-3-3 Proteins)
RN  - 0 (BAD protein, human)
RN  - 0 (BCL2L1 protein, human)
RN  - 0 (Bad protein, rat)
RN  - 0 (Bcl2l1 protein, rat)
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Carrier Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (bcl-Associated Death Protein)
RN  - 0 (bcl-X Protein)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 3.1.3.16 (Calcineurin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - 14-3-3 Proteins
MH  - Animals
MH  - *Apoptosis
MH  - Calcineurin/genetics/*metabolism
MH  - Calcineurin Inhibitors
MH  - Calcium/*metabolism/pharmacology
MH  - Carrier Proteins/chemistry/*metabolism
MH  - Cell Line
MH  - Cells, Cultured
MH  - Dimerization
MH  - Enzyme Inhibitors/pharmacology
MH  - Glutamic Acid/pharmacology
MH  - Hippocampus/cytology
MH  - Humans
MH  - Mitochondria/metabolism
MH  - Neurons/cytology/metabolism
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/metabolism
MH  - Proteins/metabolism
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Recombinant Fusion Proteins/metabolism
MH  - Transfection
MH  - *Tyrosine 3-Monooxygenase
MH  - bcl-Associated Death Protein
MH  - bcl-X Protein
EDAT- 1999/04/09 00:00
MHDA- 1999/04/09 00:01
CRDT- 1999/04/09 00:00
PHST- 1999/04/09 00:00 [pubmed]
PHST- 1999/04/09 00:01 [medline]
PHST- 1999/04/09 00:00 [entrez]
AID - 10.1126/science.284.5412.339 [doi]
PST - ppublish
SO  - Science. 1999 Apr 9;284(5412):339-43. doi: 10.1126/science.284.5412.339.