page_title: Akt/PKB signaling pathway
section_title: Phosphoinositide formation
hierarchical_section_title: Akt/PKB signaling pathway / Mechanism / Phosphoinositide formation
caption_attribution_description: The molecular structure of phosphoinositol 3,4,5-trisphosphate (PI(3,4,5)P3). The 3 phosphate groups on the inositol ring are shown in red. R1 and R2 are fatty acid chains inserted into the inner monolayer of the plasma membrane.
context_page_description: The Akt signaling pathway or PI3K-Akt signaling pathway is a signal transduction pathway that promotes survival and growth in response to extracellular signals. Key proteins involved are PI3K and Akt.
  Initial stimulation by one of the growth factors causes activation of a cell surface receptor and phosphorylation of PI3K. Activated PI3K then phosphorylates lipids on the plasma membrane, forming second messenger phosphatidylinositol-trisphosphate. Akt, a serine/threonine kinase, is recruited to the membrane by interaction with these phosphoinositide docking sites, so that it can be fully activated.
  Activated Akt mediates downstream responses, including cell survival, growth, proliferation, cell migration and angiogenesis, by phosphorylating a range of intracellular proteins. The pathway is present in all cells of higher eukaryotes and is highly conserved.
  The pathway is highly regulated by multiple mechanisms, often involving cross-talk with other signaling pathways. Problems with PI3K-Akt pathway regulation can lead to an increase in signaling activity. This has been linked to a range of diseases such as cancer and type 2 diabetes.
context_section_description: Activated PI3K catalyses the addition of phosphate groups to the 3'-OH position the inositol ring of phosphoinositides (PtdIns), producing three lipid products, PI(3)P, PI(3,4)P₂ and PI(3,4,5)P₃:
  Phosphatidylinositol (PI) → PI 3-phosphate, (PI(4)P) → PI 3,4-bisphosphate, (PI(4,5)P₂) → PI 3,4,5-triphosphate
  These phosphorylated lipids are anchored to the plasma membrane, where they can directly bind intracellular proteins containing a pleckstrin homology (PH) or FYVE domain. For example, the triphosphate form (PI(3,4,5)P₃) binds Akt and phosphoinositide-dependent kinase 1 (PDK1) so they accumulate in close proximity at the membrane.
caption: Structure of Phosphatidylinositol (3,4,5)-trisphosphate
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