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| Content Provider | PubMed Central |
|---|---|
| Author | Hauge, Camilla Antal, Torben L. Hirschberg, Daniel Doehn, Ulrik Thorup, Katrine Idrissova, Leila Hansen, Klaus Jensen, Ole N. Jørgensen, Thomas J. Biondi, Ricardo M. Morten, Frödin |
| Copyright Year | 2007 |
| Abstract | The growth factor/insulin-stimulated AGC kinases share an activation mechanism based on three phosphorylation sites. Of these, only the role of the activation loop phosphate in the kinase domain and the hydrophobic motif (HM) phosphate in a C-terminal tail region are well characterized. We investigated the role of the third, so-called turn motif phosphate, also located in the tail, in the AGC kinases PKB, S6K, RSK, MSK, PRK and PKC. We report cooperative action of the HM phosphate and the turn motif phosphate, because it binds a phosphoSer/Thr-binding site above the glycine-rich loop within the kinase domain, promoting zipper-like association of the tail with the kinase domain, serving to stabilize the HM in its kinase-activating binding site. We present a molecular model for allosteric activation of AGC kinases by the turn motif phosphate via HM-mediated stabilization of the αC helix. In S6K and MSK, the turn motif phosphate thereby also protects the HM from dephosphorylation. Our results suggest that the mechanism described is a key feature in activation of upto 26 human AGC kinases. |
| Related Links | http://dx.doi.org/10.1038/sj.emboj.7601682 |
| Ending Page | 2261 |
| Page Count | 11 |
| Starting Page | 2251 |
| File Format | |
| ISSN | 02614189 |
| e-ISSN | 14602075 |
| Journal | The EMBO Journal |
| Issue Number | 9 |
| Volume Number | 26 |
| Language | English |
| Publisher | Nature Publishing Group |
| Publisher Date | 2007-05-02 |
| Access Restriction | Open |
| Rights Holder | Nature Publishing Group |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Microbiology Medicine Molecular Biology |
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