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Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo
Open accessAbstract
3-phosphoinositide-dependent protein kinase-1 (PDK1) expressed in unstimulated 293 cells was phosphorylated at Ser-25, Ser-241, Ser-393, Ser-396 and Ser-410 and the level of phosphorylation of each site was unaffected by stimulation with insulin-like growth factor-1. Mutation of Ser-241 to Ala abolished PDK1 activity, whereas mutation of the other phosphorylation sites individually to Ala did not affect PDK1 activity. Ser-241, unlike the other phosphorylation sites on PDK1, was resistant to dephosphorylation by protein phosphatase 2A(1). Ser-241 lies in the activation loop of the PDK1 kinase domain between subdomains VII and VIII in the equivalent position to the site that PDK1 phosphorylates on its protein kinase substrates. PDK1 expressed in bacteria was active and phosphorylated at Ser-241, suggesting that PDK1 can phosphorylate itself at this site, leading to its own activation.
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Cites
Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling
SHEPHERD, P. R., WITHERS, D. J., & SIDDLE, K. (1998) · Biochemical Journal · doi:10.1042/bj3330471 · Cited by 953
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Vanhaesebroeck, B., & Alessi, D. R. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3460561 · Cited by 1,644
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Mitsuishi, Y., Taguchi, K., Kawatani, Y., Shibata, T., Nukiwa, T., Aburatani, H., Yamamoto, M., & Motohashi, H. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.05.016 · Cited by 1,395
The nuts and bolts of AGC protein kinases
Pearce, L. R., Komander, D., & Alessi, D. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2822 · Cited by 1,294
Self-citationNewton, A. C. (2001) · Chemical Reviews · doi:10.1021/cr0002801 · Cited by 962
Metadata
- Authors
- Casamayor, A., MORRICE, N. A., & Alessi, D. R.
- Venue
- Biochemical Journal
- Publisher
- Portland Press
- Published
- 1999-08-24
- Volume
- 342
- Issue
- 2
- Pages
- 287-287
- ISSN
- 0264-6021 (ISSN-L)
- OpenAlex
- W2065652048
- Cited by
- 345
- References
- 1
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Casamayor, A., MORRICE, N. A., & Alessi, D. R. (1999). Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo. Biochemical Journal. https://doi.org/10.1042/0264-6021%3A3420287
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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