Constitutive Signaling by AKT1 E17K in Cancer

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R-HSA-5674400
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Pathway
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Homo sapiens
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While AKT1 gene copy number, expression level and phosphorylation are often increased in cancer, only one low frequency point mutation has been repeatedly reported in cancer and functionally studied. This mutation represents a substitution of a glutamic acid residue with lysine at position 17 of AKT1, and acts by enabling AKT1 to bind PIP2. PIP2-bound AKT1 is phosphorylated by TORC2 complex and by PDPK1 that is always present at the plasma membrane, due to low affinity for PIP2. Therefore, E17K substitution abrogates the need for PI3K in AKT1 activation (Carpten et al. 2007, Landgraf et al. 2008).

Literature References
PubMed ID Title Journal Year
17611497 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, MHT, Blanchard, KL, Thomas, JE

Nature 2007
18954143 Molecular mechanism of an oncogenic mutation that alters membrane targeting: Glu17Lys modifies the PIP lipid specificity of the AKT1 PH domain

Landgraf, KE, Pilling, C, Falke, JJ

Biochemistry 2008
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Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
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