PI3K isoforms in cell signalling and vesicle trafficking

Nat Rev Mol Cell Biol. 2019 Sep;20(9):515-534. doi: 10.1038/s41580-019-0129-z.


PI3Ks are a family of lipid kinases that phosphorylate intracellular inositol lipids to regulate signalling and intracellular vesicular traffic. Mammals have eight isoforms of PI3K, divided into three classes. The class I PI3Ks generate 3-phosphoinositide lipids, which directly activate signal transduction pathways. In addition to being frequently genetically activated in cancer, similar mutations in class I PI3Ks have now also been found in a human non-malignant overgrowth syndrome and a primary immune disorder that predisposes to lymphoma. The class II and class III PI3Ks are regulators of membrane traffic along the endocytic route, in endosomal recycling and autophagy, with an often indirect effect on cell signalling. Here, we summarize current knowledge of the different PI3K classes and isoforms, focusing on recently uncovered biological functions and the mechanisms by which these kinases are activated. Deeper insight into the PI3K isoforms will undoubtedly continue to contribute to a better understanding of fundamental cell biological processes and, ultimately, of human disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport, Active
  • Endocytosis
  • Endosomes / metabolism*
  • Humans
  • Isoenzymes / metabolism
  • Lymphoma / enzymology*
  • Lymphoma / pathology
  • Neoplasm Proteins / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Signal Transduction*


  • Isoenzymes
  • Neoplasm Proteins