Dataset Information

Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation.

ABSTRACT: Members of the mammalian phosphoinositide-3-OH kinase (PI3K) family of proteins are critical regulators of various cellular process including cell survival, growth, proliferation, and motility. Oncogenic activating mutations in the p110alpha catalytic subunit of the heterodimeric p110/p85 PI3K enzyme are frequent in human cancers. Here we show the presence of frequent mutations in p85alpha in colon cancer, a majority of which occurs in the inter-Src homology-2 (iSH2) domain. These mutations uncouple and retain p85alpha's p110-stabilizing activity, while abrogating its p110-inhibitory activity. The p85alpha mutants promote cell survival, AKT activation, anchorage-independent cell growth, and oncogenesis in a p110-dependent manner.

SUBMITTER: Jaiswal BS

PROVIDER: S-EPMC2804903 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation.

Jaiswal Bijay S BS Janakiraman Vasantharajan V Kljavin Noelyn M NM Chaudhuri Subhra S Stern Howard M HM Wang Weiru W Kan Zhengyan Z Dbouk Hashem A HA Peters Brock A BA Waring Paul P Dela Vega Trisha T Kenski Denise M DM Bowman Krista K KK Lorenzo Maria M Li Hong H Wu Jiansheng J Modrusan Zora Z Stinson Jeremy J Eby Michael M Yue Peng P Kaminker Josh S JS de Sauvage Frederic J FJ Backer Jonathan M JM Seshagiri Somasekar S

Cancer cell 20091201 6

Members of the mammalian phosphoinositide-3-OH kinase (PI3K) family of proteins are critical regulators of various cellular process including cell survival, growth, proliferation, and motility. Oncogenic activating mutations in the p110alpha catalytic subunit of the heterodimeric p110/p85 PI3K enzyme are frequent in human cancers. Here we show the presence of frequent mutations in p85alpha in colon cancer, a majority of which occurs in the inter-Src homology-2 (iSH2) domain. These mutations unco ...[more]

PMID: 19962665

Dataset Information

Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation.

Publications

Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation.

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