Life Sciences Research for Lifelong Health

The PI3K family

There are eight different PI3K isoforms expressed by cells of our immune system. The eight different catalytic subunits have been divided into three classes based on their structure and function.

The class I PI3Ks are bound by a regulatory subunit and phosphorylate PIP2 as in the figure above. P110α and p110δ are thought to be recruited exclusively to tyrosine-kinase associated receptors.

P110γ is recruited to the plasma membrane by the Gβγ subunits that are released upon activation of G-protein-coupled receptors. P110β can be recruited to either type of receptor and probably integrates signals from both.
PI3K isoforms

signalling by lipid second messengers
The class II PI3Ks, CIIα, CIIβ and CIIγ, are not bound by regulatory subunits and are thought to mainly phosphorylate PI to generate a product with only one phosphate group: PI3P. The only class III PI3K, also called Vps34 also phosphorylated PI to generate PI3P. The role of PI3P in immune cells is only beginning to be uncovered.

PIP3 acts as a tether for signalling proteins inside the cell which relay information from outside the cells to instruct the cell how to respond. Some proteins that contain a plecstrin homology (PH) domain can bind specifically to PIP3. The most well-characterised of these are Akt (also known as PKB) and Pdk1.