![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 62, Issue 2, 225-233, August 2002
Departments of Psychiatry, and Pharmacology and Therapeutics,
Douglas Hospital Research Center, McGill University,
Montreal, Quebec, Canada
Insulin-like growth factor-1 (IGF-1) is a trophic factor promoting cell
survival by activating phosphatidylinositol 3-kinase (PI3K)/Akt kinase
pathway. FKHRL1, a member of the Forkhead family of transcription
factors possibly involved in cell cycle and apoptosis, is a downstream
target of Akt in fibroblasts. However, very little information is
available concerning neurons. We report herein that IGF-1 rapidly
induced the phosphorylation of endogenous FKHRL1 in hippocampal
neurons. The PI3K/Akt kinase pathway mediates this action, as evidenced
by the use of different kinase inhibitors, the expression of
constitutively active Akt, and in vitro kinase assay. IGF-1 blocked the
nuclear translocation of FKHRL1 in hippocampal neurons and promoted
survival in parallel to the phosphorylation of Akt and FKHRL1.
Similarly, the expression of constitutively active Akt in PC-12 cells
increased the phosphorylation of FKHRL1 and promoted survival, whereas
the expression of kinase dead Akt attenuated IGF-1-mediated survival
of PC-12 cells. Moreover, the overexpression of wild-type FKHRL1 and
its nonphosphorylated mutant induced apoptosis in cultured hippocampal
neurons. Interestingly, IGF-1 and PI3-kinase inhibitors have no
significant effect on the cell cycle inhibitor p27kip1 in hippocampal
neurons. This finding suggests that in contrast to fibroblasts, FKHRL1
is unlikely to be involved in cell cycle in neurons. Taken together,
these data reveal that endogenous FKHRL1 is a downstream substrate of PI3K/Akt in IGF-1 receptor signaling in hippocampal neurons and suggest
that the phosphorylation of this transcription factor may play an
important role in the neuronal survival properties of IGF-1.
This article has been cited by other articles:
|
|
 |
|
  G. J. Francis, J. A. Martinez, W. Q. Liu, K. Xu, A. Ayer, J. Fine, U. I. Tuor, G. Glazner, L. R. Hanson, W. H. Frey II, et al. Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy Brain, November 16, 2008; (2008) awn288v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-Q. Chen, S.-J. Wang, J.-Z. Du, and X.-C. Chen Diversities in hepatic HIF-1, IGF-I/IGFBP-1, LDH/ICD, and their mRNA expressions induced by CoCl2 in Qinghai-Tibetan plateau mammals and sea level mice Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R516 - R526. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Rasoulpour, K. DiPalma, B. Kolvek, and M. Hixon Akt1 Suppresses Radiation-Induced Germ Cell Apoptosis in Vivo Endocrinology, September 1, 2006; 147(9): 4213 - 4221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Li, K. Sampat, N. Hu, J. Zakari, and S. H. Yuspa Protein Kinase C Negatively Regulates Akt Activity and Modifies UVC-induced Apoptosis in Mouse Keratinocytes J. Biol. Chem., February 10, 2006; 281(6): 3237 - 3243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. C. Russo, P. D. Gluckman, E. L. Feldman, and G. A. Werther The Insulin-Like Growth Factor System and Its Pleiotropic Functions in Brain Endocr. Rev., December 1, 2005; 26(7): 916 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Corton and H. M. Brown-Borg Peroxisome Proliferator-Activated Receptor {gamma} Coactivator 1 in Caloric Restriction and Other Models of Longevity J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2005; 60(12): 1494 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Laurino, X. X. Wang, B. A. de la Houssaye, L. Sosa, S. Dupraz, A. Caceres, K. H. Pfenninger, and S. Quiroga PI3K activation by IGF-1 is essential for the regulation of membrane expansion at the nerve growth cone J. Cell Sci., August 15, 2005; 118(16): 3653 - 3662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Subramaniam, N. Shahani, J. Strelau, C. Laliberte, R. Brandt, D. Kaplan, and K. Unsicker Insulin-Like Growth Factor 1 Inhibits Extracellular Signal-Regulated Kinase to Promote Neuronal Survival via the Phosphatidylinositol 3-Kinase/Protein Kinase A/c-Raf Pathway J. Neurosci., March 16, 2005; 25(11): 2838 - 2852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q.-L. Cui, W.-H. Zheng, R. Quirion, and G. Almazan Inhibition of Src-like Kinases Reveals Akt-dependent and -independent Pathways in Insulin-like Growth Factor I-mediated Oligodendrocyte Progenitor Survival J. Biol. Chem., March 11, 2005; 280(10): 8918 - 8928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Xu and K. Liao Protein Kinase B/AKT 1 Plays a Pivotal Role in Insulin-like Growth Factor-1 Receptor Signaling Induced 3T3-L1 Adipocyte Differentiation J. Biol. Chem., August 20, 2004; 279(34): 35914 - 35922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Levinthal and D. B. DeFranco Transient Phosphatidylinositol 3-Kinase Inhibition Protects Immature Primary Cortical Neurons from Oxidative Toxicity via Suppression of Extracellular Signal-regulated Kinase Activation J. Biol. Chem., March 19, 2004; 279(12): 11206 - 11213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, Y. Higashi, H. Itabe, Y.-H. Song, J. Du, and P. Delafontaine Insulin-Like Growth Factor-1 Receptor Activation Inhibits Oxidized LDL-Induced Cytochrome C Release and Apoptosis via the Phosphatidylinositol 3 Kinase/Akt Signaling Pathway Arterioscler. Thromb. Vasc. Biol., December 1, 2003; 23(12): 2178 - 2184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, S. Eitan, J. Wu, C. J. Evans, B. Kieffer, X. Sun, and R. D. Polakiewicz Morphine Induces Desensitization of Insulin Receptor Signaling Mol. Cell. Biol., September 1, 2003; 23(17): 6255 - 6266. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
