Phosphoinositide 3-kinase p110 catalytic subunit (PI3K p110) (PI3K p110)

The Phosphoinositide 3-kinase (PI3K) p110 catalytic subunit is the core enzymatic component of Class I PI3Ks, responsible for phosphorylating phosphatidylinositol 4,5-bisphosphate (PIP2) to generate the second messenger phosphatidylinositol 3,4,5-trisphosphate (PIP3) [NIH, 1.2.1]. This lipid product recruits pleckstrin homology (PH) domain-containing proteins, such as AKT and PDK1, to the plasma membrane, initiating signaling cascades that regulate fundamental cellular processes including growth, proliferation, survival, and metabolism [MDPI, 1.2.2]. There are four distinct p110 isoforms—alpha, beta, delta, and gamma—each with unique tissue distributions and physiological roles [Wikipedia, 1.2.3]. Mutations or overactivation of these subunits, particularly p110α, are frequently implicated in various cancers, while p110δ and p110γ are key players in immune cell function and inflammation [NIH, 1.2.4; ResearchGate, 1.2.5]. Consequently, the p110 catalytic subunits are major therapeutic targets, with several isoform-selective and pan-PI3K inhibitors approved for treating malignancies and autoimmune conditions [NIH, 1.2.1]. However, targeting these subunits presents challenges, such as managing off-target metabolic effects like hyperglycemia and immune-related toxicities [NIH, 1.2.1].

Other names

p110PI3K catalytic subunitPIK3CAPIK3CBPIK3CDPIK3CGPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit

Inhibition of the catalytic activity of the p110 subunit, preventing the phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-trisphosphate (PIP3), thereby blocking the recruitment and activation of AKT and other downstream effectors [NIH, 1.2.1].