PI3Kgenerated

PI3Kgenerated is a term used in cell biology to describe the collection of molecular species produced by the enzymatic activity of phosphoinositide 3-kinases (PI3Ks). The concept typically centers on phosphatidylinositol 3,4,5-trisphosphate (PIP3) and related phosphoinositides that accumulate at the plasma membrane during signal transduction.

Mechanism and products: Class I PI3Ks phosphorylate phosphatidylinositol 4,5-bisphosphate (PIP2) at the 3-position to generate PIP3. PIP3 acts as a docking site for proteins with pleckstrin homology (PH) domains, such as AKT and PDK1, triggering downstream signaling pathways that govern cell growth, survival, and metabolism. The term PI3Kgenerated may be used to refer to these lipid second messengers and any closely related lipid products formed as part of the pathway.

Regulation and turnover: PI3Kgenerated species are tightly regulated by phosphatases that remove phosphate groups, notably PTEN and SHIP family enzymes. PTEN converts PIP3 back to PIP2, while SHIP enzymes can shift PIP3 to other inositol lipids, contributing to the dynamic control of signaling. Spatial and temporal localization of PI3Kgenerated lipids at the membrane influences the magnitude and duration of the response.

Clinical and research relevance: Aberrant PI3Kgenerated signaling is associated with cancer, metabolic disorders, and other diseases. Therapeutic strategies include inhibitors targeting specific PI3K isoforms to reduce abnormal production of these lipids and dampen pathogenic signaling.

Measurement and data use: Researchers quantify PI3Kgenerated lipids through lipidomics methods, such as mass spectrometry, or using fluorescent biosensors that report PIP3 localization. In databases and literature, PI3Kgenerated can serve as a descriptive label for molecules arising from PI3K activity, distinguishable from lipids formed by other pathways.