Henryk Dudek,
Sandeep Robert Datta,
*
Thomas F. Franke,
*
Morris J. Birnbaum,
Ryoji Yao,
Geoffrey M. Cooper,
Rosalind A. Segal,
David R. Kaplan,
Michael E. Greenberg
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 (p70S6K). Experiments
with pharmacological inhibitors, as well as expression of wild-type and
dominant-inhibitory forms of Akt, demonstrated that Akt but not
p70S6K 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.
H. Dudek, S. R. Datta, M. E. Greenberg, Division of Neuroscience,
Department of Neurology, Children's Hospital, and Department of
Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
T. F. Franke, Montreal Neurological Institute, McGill University, PQ
H3A 2B4, Canada; and Division of Signal Transduction, Beth Israel
Hospital, and Department of Cell Biology, Harvard Medical School,
Boston, MA 02115, USA.
M. J. Birnbaum, Howard Hughes Medical Institute, University of
Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
R. Yao and G. M. Cooper, Division of Molecular Genetics, Dana-Farber
Cancer Institute, and Department of Pathology, Harvard Medical School,
Boston, MA 02115, USA.
R. A. Segal, Department of Neurology, Beth Israel Hospital, and Harvard
Medical School, Boston, MA 02115, USA.
D. R. Kaplan, Montreal Neurological Institute, McGill University, PQ
H3A 2B4, Canada.
*
These authors made comparable contributions to this report.
To whom correspondence should be addressed.
