Phosphatidylinositol 3-kinase delta and Phosphatidylinositol 3-kinase gamma (PI3K-δ (for delta subunit), PI3K-γ (for gamma subunit))

Phosphatidylinositol 3-kinase delta (PI3K-δ) and Phosphatidylinositol 3-kinase gamma (PI3K-γ) are class I PI3K isoforms, each comprising a unique catalytic subunit (p110δ or p110γ) paired with regulatory subunits (PI3K-δ with p85 type, PI3K-γ with p101 or p84) and are primarily expressed in leukocytes[1][2][3][5][6][7]. These enzymes phosphorylate phosphoinositides at the 3’ position to generate second messengers crucial for intracellular signaling, especially in immune cells. PI3K-δ is critical for adaptive immune cell function (B-cell and T-cell activation and survival), whereas PI3K-γ regulates innate immunity, chemotaxis, and inflammatory signaling[6][7]. Both are validated therapeutic targets in hematologic cancers and inflammatory/autoimmune diseases, with several drugs developed as inhibitors. Selective and dual inhibitors have advanced to clinical use, but adverse effects related to immune modulation are significant clinical challenges[6][7].

Other names

PI3K deltaPI3K gammap110δ (delta catalytic subunit)p110γ (gamma catalytic subunit)PIK3CD (gene encoding delta isoform)PIK3CG (gene encoding gamma isoform)

Inhibition of kinase activity reduces PI3K-mediated signaling; Blockade of PI3K-δ impairs survival and proliferation of malignant leukocytes; Blockade of PI3K-γ impairs myeloid cell-mediated immune suppression; Modulation of immune cell trafficking, activation, and cytokine production