PMID- 10576741
OWN - NLM
STAT- MEDLINE
DCOM- 19991214
LR  - 20190619
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 286
IP  - 5445
DP  - 1999 Nov 26
TI  - Differentiation stage-specific inhibition of the Raf-MEK-ERK pathway by Akt.
PG  - 1738-41
AB  - Extracellular signals often result in simultaneous activation of both the
      Raf-MEK-ERK and PI3K-Akt pathways (where ERK is extracellular-regulated kinase,
      MEK is mitogen-activated protein kinase or ERK kinase, and PI3K is
      phosphatidylinositol 3-kinase). However, these two signaling pathways were shown 
      to exert opposing effects on muscle cell hypertrophy. Furthermore, the PI3K-Akt
      pathway was shown to inhibit the Raf-MEK-ERK pathway; this cross-regulation
      depended on the differentiation state of the cell: Akt activation inhibited the
      Raf-MEK-ERK pathway in differentiated myotubes, but not in their myoblast
      precursors. The stage-specific inhibitory action of Akt correlated with its
      stage-specific ability to form a complex with Raf, suggesting the existence of
      differentially expressed mediators of an inhibitory Akt-Raf complex.
FAU - Rommel, C
AU  - Rommel C
AD  - Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
FAU - Clarke, B A
AU  - Clarke BA
FAU - Zimmermann, S
AU  - Zimmermann S
FAU - Nunez, L
AU  - Nunez L
FAU - Rossman, R
AU  - Rossman R
FAU - Reid, K
AU  - Reid K
FAU - Moelling, K
AU  - Moelling K
FAU - Yancopoulos, G D
AU  - Yancopoulos GD
FAU - Glass, D J
AU  - Glass DJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Cdkn1a protein, mouse)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Myog protein, mouse)
RN  - 0 (Myogenin)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Line
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/genetics
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism
MH  - Muscle, Skeletal/*cytology/*metabolism
MH  - Myogenin/genetics
MH  - Phenotype
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Proto-Oncogene Proteins c-raf/*antagonists & inhibitors/metabolism
MH  - Signal Transduction
MH  - Transfection
MH  - Transgenes
EDAT- 1999/11/27 00:00
MHDA- 1999/11/27 00:01
CRDT- 1999/11/27 00:00
PHST- 1999/11/27 00:00 [pubmed]
PHST- 1999/11/27 00:01 [medline]
PHST- 1999/11/27 00:00 [entrez]
AID - 8036 [pii]
AID - 10.1126/science.286.5445.1738 [doi]
PST - ppublish
SO  - Science. 1999 Nov 26;286(5445):1738-41. doi: 10.1126/science.286.5445.1738.