title: 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.
authors: Department of Molecular Biology, Genentech Inc., South San Francisco, CA 94080, USA.
authors: Bijay S
authors: BS
authors: Jaiswal
authors: Vasantharajan
authors: V
authors: Janakiraman
authors: Noelyn M
authors: NM
authors: Kljavin
authors: Subhra
authors: S
authors: Chaudhuri
authors: Howard M
authors: HM
authors: Stern
authors: Weiru
authors: W
authors: Wang
authors: Zhengyan
authors: Z
authors: Kan
authors: Hashem A
authors: HA
authors: Dbouk
authors: Brock A
authors: BA
authors: Peters
authors: Paul
authors: P
authors: Waring
authors: Trisha
authors: T
authors: Dela Vega
authors: Denise M
authors: DM
authors: Kenski
authors: Krista K
authors: KK
authors: Bowman
authors: Maria
authors: M
authors: Lorenzo
authors: Hong
authors: H
authors: Li
authors: Jiansheng
authors: J
authors: Wu
authors: Zora
authors: Z
authors: Modrusan
authors: Jeremy
authors: J
authors: Stinson
authors: Michael
authors: M
authors: Eby
authors: Peng
authors: P
authors: Yue
authors: Josh S
authors: JS
authors: Kaminker
authors: Frederic J
authors: FJ
authors: de Sauvage
authors: Jonathan M
authors: JM
authors: Backer
authors: Somasekar
authors: S
authors: Seshagiri
mesh_terms: D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology*; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D019869:Phosphatidylinositol 3-Kinases