Rare cancer-specific mutations in PIK3CA show gain of function.

ABSTRACT: Fifteen rare cancer-derived mutants of PIK3CA, the gene coding for the catalytic subunit p110alpha of phosphatidylinositol 3-kinase (PI3K), were examined for their biological and biochemical properties. Fourteen of these mutants show a gain of function: they induce rapamycin-sensitive oncogenic transformation of chicken embryo fibroblasts, constitutively activate Akt and TOR-mediated signaling, and show enhanced lipid kinase activity. Mapping of these mutants on a partial structural model of p110alpha suggests three groups of mutants, defined by their location in distinct functional domains of the protein. We hypothesize that each of these three groups induces a gain of PI3K function by a different molecular mechanism. Mutants in the C2 domain increase the positive surface charge of this d

SUBMITTER: Gymnopoulos M 

PROVIDER: S-EPMC1838453 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature