2uzs

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{{STRUCTURE_2uzs| PDB=2uzs | SCENE= }}
{{STRUCTURE_2uzs| PDB=2uzs | SCENE= }}
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'''A TRANSFORMING MUTATION IN THE PLECKSTRIN HOMOLOGY DOMAIN OF AKT1 IN CANCER (AKT1-PH_E17K)'''
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===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.
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(as it appears on PubMed at http://www.pubmed.gov), where 17611497 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17611497}}
==About this Structure==
==About this Structure==
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[[Category: Translation regulation]]
[[Category: Translation regulation]]
[[Category: Transport]]
[[Category: Transport]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 17:53:36 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 00:40:16 2008''

Revision as of 21:40, 28 July 2008

Image:2uzs.png

Template:STRUCTURE 2uzs

A TRANSFORMING MUTATION IN THE PLECKSTRIN HOMOLOGY DOMAIN OF AKT1 IN CANCER (AKT1-PH_E17K)

Template:ABSTRACT PUBMED 17611497

About this Structure

2UZS is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

A transforming mutation in the pleckstrin homology domain of AKT1 in cancer., Carpten JD, Faber AL, Horn C, Donoho GP, Briggs SL, Robbins CM, Hostetter G, Boguslawski S, Moses TY, Savage S, Uhlik M, Lin A, Du J, Qian YW, Zeckner DJ, Tucker-Kellogg G, Touchman J, Patel K, Mousses S, Bittner M, Schevitz R, Lai MH, Blanchard KL, Thomas JE, Nature. 2007 Jul 26;448(7152):439-44. Epub 2007 Jul 4. PMID:17611497

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