Publication Date:
1999-11-27
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rommel, C -- Clarke, B A -- Zimmermann, S -- Nunez, L -- Rossman, R -- Reid, K -- Moelling, K -- Yancopoulos, G D -- Glass, D J -- New York, N.Y. -- Science. 1999 Nov 26;286(5445):1738-41.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10576741" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Differentiation
;
Cell Line
;
Cyclin-Dependent Kinase Inhibitor p21
;
Cyclins/genetics
;
Enzyme Activation
;
Enzyme Inhibitors/pharmacology
;
Flavonoids/pharmacology
;
Insulin-Like Growth Factor I/pharmacology
;
MAP Kinase Signaling System/drug effects
;
Mice
;
Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism
;
Muscle, Skeletal/*cytology/*metabolism
;
Myogenin/genetics
;
Phenotype
;
Phosphatidylinositol 3-Kinases/metabolism
;
Phosphorylation
;
Protein-Serine-Threonine Kinases/*metabolism
;
Proto-Oncogene Proteins/*metabolism
;
Proto-Oncogene Proteins c-akt
;
Proto-Oncogene Proteins c-raf/*antagonists & inhibitors/metabolism
;
Signal Transduction
;
Transfection
;
Transgenes
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink