PIP2

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a minor but essential phospholipid component of the inner leaflet of the plasma membrane. It consists of a glycerol backbone with two fatty acyl chains and a phosphatidylinositol headgroup bearing phosphate groups at the 4 and 5 positions of the inositol ring. PIP2 participates in numerous signaling and membrane dynamics processes by serving as a substrate and a binding partner for diverse proteins.

Biosynthesis and turnover: PIP2 is primarily formed by phosphorylation of phosphatidylinositol 4-phosphate (PI4P) at the 5 position by PI(4)P 5-kinases. It can be phosphorylated further by phosphoinositide 3-kinases (PI3K) to form phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP2 is rapidly hydrolyzed by phospholipase C (PLC) to yield diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). The lipid is also dephosphorylated by phosphatases such as PTEN, which converts PIP3 back to PIP2, helping regulate signaling balance.

Functions: PIP2 helps recruit and regulate a range of signaling and cytoskeletal proteins, especially those with PH, ENTH, or C2 domains. It is a key substrate in PLC signaling, linking receptor activation to IP3-triggered Ca2+ release and DAG-mediated activation of protein kinase C and other effectors. PIP2 also modulates membrane trafficking, endocytosis, and actin dynamics by coordinating interactions with actin-binding proteins and endocytic machinery.

Regulation: Cellular PIP2 levels are tightly controlled by kinases and phosphatases, including PI4P 5-kinases, PI3K, PTEN, and various phosphatases. Localized pools of PIP2 can be maintained or depleted in membrane microdomains, enabling spatially specific signaling and cytoskeletal remodeling.

See also: PI3K/AKT pathway, phospholipase C, PH domain, PTEN.