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Literature summary for 2.7.1.153 extracted from

  • Zhao, L.; Vogt, P.K.
    Helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms (2008), Proc. Natl. Acad. Sci. USA, 105, 2652-2657.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
RAS-GTP regulatory domain p85 interacts with RAS-GTP. RAS binding is essential for oncogenic transformation by helical domain mutants of p110alpha Homo sapiens

Protein Variants

Protein Variants Comment Organism
E542K/E545K gain-of-function helical domain mutations result in upregulation of enzyme activity, Akt phosphorylation and cell transformation Homo sapiens
E545K/H1047R gain-of-function helical domain mutations result in upregulation of enzyme activity, Akt phosphorylation and cell transformation Homo sapiens
H1047R gain-of-function mutation of subunit p110alpha, the H1047R mutation can substitute for RAS binding, but binding to p85 is essential for H1047R-induced cell transformation Homo sapiens
K227E the mutaion reduces enzyme activity Homo sapiens
additional information helical domain and kinase domain mutations in p110alpha of phosphatidylinositol 3-kinase induce gain of function by different mechanisms, overview. About 30% of prostate, breast, cervix, and endometrium tumors show catalytic subunit p110alpha mutations, the most prominent single amino acid substitutions in the helical or kinase domain result in a gain of enzymatic function, activate AKT signaling, and induce oncogenic transformation, analysis of hot-spot mutations in gene PIK3CA. The gain of function induced by helical domain mutations is independent of binding to p85 but requires interaction with RAS-GTP. In contrast, the kinase domain mutation is active in the absence of RAS-GTP binding but is highly dependent on the interaction with p85. Truncation reduce the activities of all enzymes, truncated wild-type and mutant, overview. Phenotypes, overview Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
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gene PIK3CA encoding for the catalytic subunit p110alpha of PI3K
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Source Tissue

Source Tissue Comment Organism Textmining
breast cancer cell
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Homo sapiens
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cervical carcinoma cell
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Homo sapiens
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endometrial cancer cell line
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Homo sapiens
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prostate cancer cell line
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Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information regulatory domain p85 interacts with RAS-GTP Homo sapiens ?
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?

Subunits

Subunits Comment Organism
heterodimer catalytic subunit p110alpha and regulatory subunit p85. p85 binding to p110alpha is required for activity Homo sapiens

Synonyms

Synonyms Comment Organism
PI3K
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Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
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Homo sapiens

General Information

General Information Comment Organism
metabolism PI3K is part of the PI3K signaling pathway that is upregulated in cancer Homo sapiens