The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1
Open accessAbstract
Although genetic analysis has demonstrated that members of the winged helix, or forkhead, family of transcription factors play pivotal roles in the regulation of cellular differentiation and proliferation, both during development and in the adult, little is known of the mechanisms underlying their regulation. Here we show that the activation of phosphatidylinositol 3 (PI3) kinase by extracellular growth factors induces phosphorylation, nuclear export, and transcriptional inactivation of FKHR1, a member of the FKHR subclass of the forkhead family of transcription factors. Protein kinase B (PKB)/Akt, a key mediator of PI3 kinase signal transduction, phosphorylated recombinant FKHR1 in vitro at threonine-24 and serine-253. Mutants FKHR1(T24A), FKHR1(S253A), and FKHR1(T24A/S253A) were resistant to both PKB/Akt-mediated phosphorylation and PI3 kinase-stimulated nuclear export. These results indicate that phosphorylation by PKB/Akt negatively regulates FKHR1 by promoting export from the nucleus.
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Cites
Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995) · Nature · doi:10.1038/378785a0 · Cited by 5,244
Cited by
Cellular survival: a play in three Akts
Datta, S. R., Brunet, A., & Greenberg, M. E. (1999) · Genes & Development · doi:10.1101/gad.13.22.2905 · Cited by 4,216
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239
The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation
Mendoza, M. C., Er, E. E., & Blenis, J. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2011.03.006 · Cited by 1,817
The PI3K‒PDK1 connection: more than just a road to PKB
Vanhaesebroeck, B., & Alessi, D. R. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3460561 · Cited by 1,644
FoxOs Are Critical Mediators of Hematopoietic Stem Cell Resistance to Physiologic Oxidative Stress
Tothova, Z., Kollipara, R., Huntly, B. J., Lee, B. H., Castrillon, D. H., Cullen, D. E., McDowell, E. P., Lazo-Kallanian, S., Williams, I. R., Sears, C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.01.003 · Cited by 1,562
Metadata
- Authors
- Biggs, W. H., Meisenhelder, J., Hunter, T., Cavenee, W. K., & Arden, K. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-06-22
- Volume
- 96
- Issue
- 13
- Pages
- 7421-7426
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1979147887
- Cited by
- 1,116
- References
- 1
- FWCI
- 16.31
- Type
- journal article
- Language
- en
- Open access
- green
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- Biggs, W. H., Meisenhelder, J., Hunter, T., Cavenee, W. K., & Arden, K. C. (1999). Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.96.13.7421
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