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Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase regulates cell signaling and survival.
Ueki, Kohjiro; Fruman, David A; Brachmann, Saskia M; Tseng, Yu-Hua; Cantley, Lewis C; Kahn, C Ronald.
Afiliação
  • Ueki K; Research Division, Joslin Diabetes Center, Harvard Medical School. Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Mol Cell Biol ; 22(3): 965-77, 2002 Feb.
Article em En | MEDLINE | ID: mdl-11784871
ABSTRACT
Class Ia phosphoinositide (PI) 3-kinase is a central component in growth factor signaling and is comprised of a p110 catalytic subunit and a regulatory subunit, the most common family of which is derived from the p85alpha gene (Pik3r1). Optimal signaling through the PI 3-kinase pathway depends on a critical molecular balance between the regulatory and catalytic subunits. In wild-type cells, the p85 subunit is more abundant than p110, leading to competition between the p85 monomer and the p85-p110 dimer and ineffective signaling. Heterozygous disruption of Pik3r1 results in increased Akt activity and decreased apoptosis by insulin-like growth factor 1 (IGF-1) through up-regulated phosphatidylinositol (3,4,5)-triphosphate production. Complete depletion of p85alpha, on the other hand, results in significantly increased apoptosis due to reduced PI 3-kinase-dependent signaling. Thus, a reduction in p85alpha represents a novel therapeutic target for enhancing IGF-1/insulin signaling, prolongation of cell survival, and protection against apoptosis.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfatidilinositol 3-Quinases Limite: Animals Idioma: En Revista: Mol Cell Biol Ano de publicação: 2002 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fosfatidilinositol 3-Quinases Limite: Animals Idioma: En Revista: Mol Cell Biol Ano de publicação: 2002 Tipo de documento: Article País de afiliação: Estados Unidos