Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation
| Autor: | Morten Frödin, Daniel Hirschberg, Leila Idrissova, Torben L. Antal, Klaus Hansen, Ole N. Jensen, Ricardo M. Biondi, Katrine Thorup, Ulrik Doehn, Camilla Hauge, Thomas J. D. Jørgensen |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Allosteric regulation Amino Acid Motifs Hydrophobicity Molecular Sequence Data P70-S6 Kinase 1 Biology Protein Serine-Threonine Kinases General Biochemistry Genetics and Molecular Biology Article Protein Structure Secondary Dephosphorylation Humans Amino Acid Sequence Phosphorylation Molecular Biology Protein kinase C Protein-Serine-Threonine Kinases Binding Sites General Immunology and Microbiology General Neuroscience Cell biology Enzyme Activation Biochemistry Protein kinase domain Intercellular Signaling Peptides and Proteins Signal transduction Hydrophobic and Hydrophilic Interactions Signal Transduction |
| Zdroj: | Hauge, C, Antal, T L, Hirschberg, D, Doehn, U, Thorup, K, Idrissova, L, Hansen, K, Jensen, O N, Jørgensen, T J, Biondi, R M & Frödin, M 2007, ' Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation ', EMBO Journal, vol. 26, no. 9, pp. 2251-2261 . https://doi.org/10.1038/sj.emboj.7601682 |
| DOI: | 10.1038/sj.emboj.7601682 |
| Popis: | Udgivelsesdato: 2007-May-2 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 alphaC 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. |
| Databáze: | OpenAIRE |
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