Phosphatidylinositol-3 kinase

Phosphatidylinositol-3 Kinase

Phosphatidylinositol-3 kinase (PI3K) is a family of enzymes involved in cellular functions such as growth, proliferation, differentiation, motility, survival, and intracellular trafficking. These enzymes are a part of the phosphoinositide 3-kinase pathway, which is significant in cancer and other diseases.

Structure

PI3Ks are heterodimeric proteins composed of a regulatory subunit and a catalytic subunit. The catalytic subunit is responsible for the kinase activity, while the regulatory subunit modulates the activity of the catalytic subunit. There are three classes of PI3Ks:

• Class I PI3Ks: These are the most studied and are activated by receptor tyrosine kinases (RTKs) and G protein-coupled receptors (GPCRs). They are involved in the production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3).
• Class II PI3Ks: These are less well understood and are involved in the production of phosphatidylinositol (3,4)-bisphosphate (PI(3,4)P2).
• Class III PI3Ks: These are involved in the regulation of autophagy and the production of phosphatidylinositol 3-phosphate (PI3P).

Function

PI3Ks phosphorylate the 3' hydroxyl group of the inositol ring of phosphatidylinositol lipids. This phosphorylation event is crucial for the activation of downstream signaling pathways, including the Akt/PKB signaling pathway.

The PI3K/Akt pathway is involved in regulating the cell cycle and is directly related to cellular quiescence, proliferation, cancer, and longevity. Dysregulation of this pathway can lead to oncogenesis, making PI3K a target for cancer therapy.

Clinical Significance

Mutations in PI3K genes, such as PIK3CA, are common in various types of cancer, including breast cancer, colorectal cancer, and glioblastoma. Inhibitors targeting PI3K are being developed and tested in clinical trials as potential cancer therapies.

PI3K inhibitors, such as idelalisib and copanlisib, have been approved for the treatment of certain types of leukemia and lymphoma.

Research and Development

Ongoing research is focused on understanding the specific roles of different PI3K isoforms in various cellular processes and diseases. This research aims to develop more selective and effective PI3K inhibitors with fewer side effects.

Also see

• Phosphoinositide 3-kinase pathway
• Akt/PKB signaling pathway
• Receptor tyrosine kinase
• G protein-coupled receptor
• Cancer therapy