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| {{STRUCTURE_2uzr| PDB=2uzr | SCENE= }} | | {{STRUCTURE_2uzr| PDB=2uzr | SCENE= }} |
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| '''A TRANSFORMING MUTATION IN THE PLECKSTRIN HOMOLOGY DOMAIN OF AKT1 IN CANCER (AKT1-PH_E17K)'''
| | ===A TRANSFORMING MUTATION IN THE PLECKSTRIN HOMOLOGY DOMAIN OF AKT1 IN CANCER (AKT1-PH_E17K)=== |
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| ==Overview==
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| Although AKT1 (v-akt murine thymoma viral oncogene homologue 1) kinase is a central member of possibly the most frequently activated proliferation and survival pathway in cancer, mutation of AKT1 has not been widely reported. Here we report the identification of a somatic mutation in human breast, colorectal and ovarian cancers that results in a glutamic acid to lysine substitution at amino acid 17 (E17K) in the lipid-binding pocket of AKT1. Lys 17 alters the electrostatic interactions of the pocket and forms new hydrogen bonds with a phosphoinositide ligand. This mutation activates AKT1 by means of pathological localization to the plasma membrane, stimulates downstream signalling, transforms cells and induces leukaemia in mice. This mechanism indicates a direct role of AKT1 in human cancer, and adds to the known genetic alterations that promote oncogenesis through the phosphatidylinositol-3-OH kinase/AKT pathway. Furthermore, the E17K substitution decreases the sensitivity to an allosteric kinase inhibitor, so this mutation may have important clinical utility for AKT drug development.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17611497}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17611497 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17611497}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Translation regulation]] | | [[Category: Translation regulation]] |
| [[Category: Transport]] | | [[Category: Transport]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 17:53:39 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 04:52:53 2008'' |