The PI3K isoform can be activated by insulin via the insulin receptor to initiate a cascade of events that control cell growth and metabolism. The activation of PI3K is mediated by the p85 regulatory subunit binding to tyrosine phosphorylated insulin receptor substrate (IRS) proteins (e.g. IRS-1 and IRS-2). It was also shown that PI3K is involved in apoptosis in human colon carcinoma cells. Injection of neutralizing antibodies specific to p110 in WiDr, HCT116 and CO115 adenocarcinoma cells inhibited de novo DNA synthesis PI3K is the major PI3K isoform required for apoptotic cell and Fc-receptor mediated phagocytosis shown for primary mouse macrophages and the Jurkat human leukemia T cell line. It was shown by several research groups that the catalytic subunit of PI3K can be activated by G subunits of G-protein coupled receptors.
Phosphoinositide 3-kinases (PI3Ks) phosphorylate phosphatidylinositols (PIs) at their 3´-OH position generating lipid second messengers and thereby regulate numerous biological processes including cell growth, differentiation, survival, proliferation, migration andmetabolism. On the basis of structural similarities and substrate specificity, the PI3K family can be subdivided into three classes termed I, II, and III. All human class I members are heterodimers consisting of a catalytic subunit (MW approx. 110kD) and a noncatalytic subunit (MW 50, 55, 85, or 101kD) and are known to phosphorylate phosphatidylinositol (PI), phosphatidylinositol-4-mono-phosphate (PIP) and phosphatidylinositol-4,5-bisphosphate (PIP2) in vitro. The class I members can be further subdivided into class IA and IB PI3Ks. Class IA exists in three isoforms p110 , p110 and p110 ) whereas the only class IB member is termed p110
Class IA PI3Ks are activated by adaptor proteins such as Ras or BCAP, or -kinase-associated receptors including antigen, co-stimulatory and cytokine receptors e.g. CD19, CD28, Insulin receptor, EGFR, and PDGFR). p110 is activated by G-protein-coupled receptors (GPCRs). Effectors of class I PI3Ks are pleckstrin-homology domain proteins such as Akt/PKB, BTK, TEC, ITK, BAM32, and small GTPases (e.g. Cdc42, Rac, or Ras). The action of PI3Ks is regulated by the phosphatidylinositol- 3,4,5-trisphosphate phosphatases SHIP and PTEN.
Activity: ~3nmol/mg/min using phosphatidylinositol as the substrate.
Molecular weight:p110b: 124.3kDp85a: 83.6kD
Store: For long-term storage, aliquot and store at -20°C. Aliquots are stable for at least 6 months at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
