PIK3CB

PIK3CB is the gene encoding the beta isoform of the catalytic subunit of class I phosphoinositide 3-kinases, commonly referred to as p110β. The encoded protein forms a catalytic subunit that, in complex with regulatory p85 subunits, phosphorylates phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3) at the plasma membrane. This lipid product recruits and activates downstream signaling proteins such as AKT, initiating pathways that regulate cell growth, survival, metabolism, and cytoskeletal organization.

PIK3CB activity is stimulated by receptor tyrosine kinases and G protein-coupled receptors, and it can contribute to signaling in cells with reduced PTEN activity, leading to accumulation of PIP3. Physiologically, PI3Kβ participates in insulin signaling, platelet activation, and immune cell signaling, among other processes.

In cancer biology, PIK3CB alterations are less common than those of PIK3CA but can contribute to tumorigenesis, particularly in PTEN-deficient contexts where PI3Kβ supports survival signaling. This has motivated the development of selective p110β inhibitors for research and potential therapy; examples studied in preclinical models include TGX-221 and GSK2636771. Clinical development has faced challenges due to redundancy with other PI3K isoforms and adverse effects.

Structurally, p110β contains a Ras-binding domain, a C2 domain, a helical region, and a C-terminal kinase domain. It associates with regulatory subunits such as p85, and its activity is opposed by phosphatases PTEN and SHIP that dephosphorylate PIP3. PIK3CB is one of the four catalytic subunits of class I PI3Ks, with PIK3CA, PIK3CD, and PIK3CG as paralogs that have distinct tissue distributions and regulatory properties.