Disease relevance of PIK3CA

• Indeed, transfection with adenovirus containing endothelial cell NO synthase (eNOS) or protein kinase G (PKG) increased endothelial cell migration, which was inhibited by cotransfection with a dominant-negative mutant of PI3 kinase (dnPI3 kinase) [1].
• The phosphatidylinositol 3-kinase (PI3-K)/Akt pathway is involved in various malignancies, but the role of PI3-K/Akt pathway in Epstein-Barr virus (EBV) infected Burkitt's lymphoma (BL) cells remains unclear [2].

High impact information on PIK3CA

• The angiogenic program is regulated by extracellular factors, whose input is integrated at least in part at the level of signal transduction pathways driven by phosphoinositide 3 kinase (PI3K) and phospholipase Cgamma (PLCgamma) [3].
• The underlying mechanism by which PLCgamma antagonized tube formation appeared to be by competing with PI3K for their common substrate, phosphatidylinositol-4,5-bisphosphate [3].
• Both GSNO and SNAP increased Akt phosphorylation and activity, which were blocked by cotreatment with the PI3 kinase inhibitor wortmannin [1].
• These findings indicate that NO promotes endothelial cell migration and neovascularization via cGMP-dependent activation of PI3 kinase and suggest that this pathway is important in mediating NO-induced angiogenesis [1].
• The mechanism was due to the activation of soluble guanylyl cyclase because 8-bromo-cyclic GMP activated PI3 kinase and the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ) blocked NO-induced PI3 kinase activity [1].

Biological context of PIK3CA

• Enhancement of insulin-induced PI3K/Akt/GSK-3beta and ERK signaling by neuronal nicotinic receptor/PKC-alpha/ERK pathway: up-regulation of IRS-1/-2 mRNA and protein in adrenal chromaffin cells [4].
• Actions of IGF-I to increase cell number were blocked by treatment with the mitogen activated protein kinase kinase (MAPKK) inhibitor PD 98059 whereas the phosphatidylinositol 3-kinase (PI3K) inhibitor LY 294002 had no effect [5].
• These results demonstrate that PI3-K/Akt pathway is activated constitutively in P3HR-1 cells; it promotes cell growth and the lytic cycle cascade downstream of ZEBRA [2].

Anatomical context of PIK3CA

• We have found that alpha-actinin copurifies with PI 3-kinase from bovine thymus [6].
• The antibody against PI 3-kinase 85 kDa subunit (p85) also co-immunoprecipitates alpha-actinin from lysates of NIH/3T3 cells [6].
• Insulin-like growth factor-I promotes resistance of bovine preimplantation embryos to heat shock through actions independent of its anti-apoptotic actions requiring PI3K signaling [5].
• To elucidate therapeutic targets for BL, this study investigates the effect of PI3-K/Akt pathway in: EBV-positive BL cell lines Raji, P3HR-1, Akata and Daudi; and EBV-negative BL cell lines Ramos and BJAB [2].
• Transcription factor Ets-1 regulates fibroblast growth factor-1-mediated angiogenesis in vivo: role of Ets-1 in the regulation of the PI3K/AKT/MMP-1 pathway [7].

Associations of PIK3CA with chemical compounds

• In these cells, insulin-induced tyrosine phosphorylation of IRS-1/IRS-2 and recruitment of phosphoinositide 3-kinase (PI3K) to IRS-1/IRS-2 were augmented by approximately 63% [4].
• Pretreatment with a range of other PI3 kinase inhibitors, including wortmannin and LY294002, showed no effects [8].
• Serine 1179 phosphorylation of endothelial nitric oxide synthase caused by 2,4,6-trinitrotoluene through PI3K/Akt signaling in endothelial cells [9].
• PTEN (also known as MMAC1/TEP1) is a lipid phosphatase that leads to a decrease in intracellular phosphatidylinositol 3,4,5 trisphosphate (PIP3) and therefore can modulate the stimulating effect of phosphatidylinositol 3-kinase (PI3K) [10].
• These results suggest that TNT affects NADPH oxidase, thereby generating hydrogen peroxide, which is capable of activating PI3K/Akt signaling associated with eNOS Ser 1179 phosphorylation [9].

References