PMID- 10558990
OWN - NLM
STAT- MEDLINE
DCOM- 19991130
LR  - 20190619
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 286
IP  - 5443
DP  - 1999 Nov 12
TI  - Cell survival promoted by the Ras-MAPK signaling pathway by
      transcription-dependent and -independent mechanisms.
PG  - 1358-62
AB  - A mechanism by which the Ras-mitogen-activated protein kinase (MAPK) signaling
      pathway mediates growth factor-dependent cell survival was characterized. The
      MAPK-activated kinases, the Rsks, catalyzed the phosphorylation of the
      pro-apoptotic protein BAD at serine 112 both in vitro and in vivo. The
      Rsk-induced phosphorylation of BAD at serine 112 suppressed BAD-mediated
      apoptosis in neurons. Rsks also are known to phosphorylate the transcription
      factor CREB (cAMP response element-binding protein) at serine 133. Activated CREB
      promoted cell survival, and inhibition of CREB phosphorylation at serine 133
      triggered apoptosis. These findings suggest that the MAPK signaling pathway
      promotes cell survival by a dual mechanism comprising the posttranslational
      modification and inactivation of a component of the cell death machinery and the 
      increased transcription of pro-survival genes.
FAU - Bonni, A
AU  - Bonni A
AD  - Division of Neuroscience, Children's Hospital, and Department of Neurobiology,
      Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
FAU - Brunet, A
AU  - Brunet A
FAU - West, A E
AU  - West AE
FAU - Datta, S R
AU  - Datta SR
FAU - Takasu, M A
AU  - Takasu MA
FAU - Greenberg, M E
AU  - Greenberg ME
LA  - eng
GR  - NIHP30-HD18655/HD/NICHD NIH HHS/United States
GR  - P01 HD 24926/HD/NICHD NIH HHS/United States
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 (Bad protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (bcl-Associated Death Protein)
RN  - 17885-08-4 (Phosphoserine)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
CIN - Science. 1999 Nov 12;286(5443):1309-10. PMID: 10610536
MH  - Animals
MH  - *Apoptosis
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Carrier Proteins/genetics/metabolism
MH  - *Cell Survival
MH  - Cells, Cultured
MH  - Cerebellum/cytology
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - MAP Kinase Kinase 1
MH  - *MAP Kinase Signaling System
MH  - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - Mutation
MH  - Neurons/*cytology/metabolism
MH  - Phosphorylation
MH  - Phosphoserine/metabolism
MH  - *Protein-Serine-Threonine Kinases
MH  - Rats
MH  - Rats, Long-Evans
MH  - Recombinant Fusion Proteins/metabolism
MH  - Ribosomal Protein S6 Kinases/genetics/*metabolism
MH  - *Transcription, Genetic
MH  - Transfection
MH  - bcl-Associated Death Protein
MH  - ras Proteins/metabolism
EDAT- 1999/11/13 00:00
MHDA- 1999/11/13 00:01
CRDT- 1999/11/13 00:00
PHST- 1999/11/13 00:00 [pubmed]
PHST- 1999/11/13 00:01 [medline]
PHST- 1999/11/13 00:00 [entrez]
AID - 7993 [pii]
AID - 10.1126/science.286.5443.1358 [doi]
PST - ppublish
SO  - Science. 1999 Nov 12;286(5443):1358-62. doi: 10.1126/science.286.5443.1358.