Publication Date:
1997-01-31
Description:
A signaling pathway was delineated by which insulin-like growth factor 1 (IGF-1) promotes the survival of cerebellar neurons. IGF-1 activation of phosphoinositide 3-kinase (PI3-K) triggered the activation of two protein kinases, the serine-threonine kinase Akt and the p70 ribosomal protein S6 kinase (p70(S6K)). Experiments with pharmacological inhibitors, as well as expression of wild-type and dominant-inhibitory forms of Akt, demonstrated that Akt but not p70(S6K) mediates PI3-K-dependent survival. These findings suggest that in the developing nervous system, Akt is a critical mediator of growth factor-induced neuronal survival.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dudek, H -- Datta, S R -- Franke, T F -- Birnbaum, M J -- Yao, R -- Cooper, G M -- Segal, R A -- Kaplan, D R -- Greenberg, M E -- DK39519/DK/NIDDK NIH HHS/ -- R01 CA18689/CA/NCI NIH HHS/ -- R01 CA43855/CA/NCI NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1997 Jan 31;275(5300):661-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, Children's Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9005851" target="_blank"〉PubMed〈/a〉
Keywords:
Androstadienes/pharmacology
;
Animals
;
*Apoptosis/drug effects
;
Calcium-Calmodulin-Dependent Protein Kinases/metabolism
;
Cell Survival/drug effects
;
Cells, Cultured
;
Cerebellum/cytology
;
Chromones/pharmacology
;
Enzyme Activation
;
Enzyme Inhibitors/pharmacology
;
Insulin/pharmacology
;
Insulin-Like Growth Factor I/*pharmacology
;
Morpholines/pharmacology
;
Neurons/*cytology/drug effects/enzymology
;
Phosphatidylinositol 3-Kinases
;
Phosphotransferases (Alcohol Group Acceptor)/metabolism
;
Protein-Serine-Threonine Kinases/*metabolism
;
Proto-Oncogene Proteins/chemistry/genetics/*metabolism
;
Proto-Oncogene Proteins c-akt
;
Rats
;
Ribosomal Protein S6 Kinases
;
*Signal Transduction
;
Transfection
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
