PI 3-kinases and lipid messengers

Published on August 31, 2020   45 min

A selection of talks on Biochemistry

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Hello and welcome everybody. My name is Bart Vanhaesebroeck. I work at University College London in the United Kingdom. Today we will talk about PI 3-kinases. I have been involved in this field for about 20 years, so I'm pleased today to be able to provide this introduction to you.
We will talk about PI 3-kinases or PI3K in short. What PI 3-kinases do, they are signal transduction molecules that sit in the cytoplasm of cells. They become recruited in the cell membrane and then they phosphorylate, they add a phosphate to a lipid in the cell membranes. The lipid is called a PI lipid. That phosphorylated lipid then interacts with different proteins, proteins x, y, and z. This changes the function and the localisation of these proteins and induces cell signalling and controls intracellular vesicular traffic. In short, PI 3-kinases phosphorylate membrane lipids. These membrane lipids then bind lipid-binding proteins and that generates a biological output. PI 3-kinases are also involved in disease, chiefly in cancer, immune dysregulation, overgrowth syndromes, metabolic diseases, and neurobiology and several others.
Here is a more detailed overview of today's presentation. We will start with a large part of basic science where I will explain to you what these PI lipids are about. They form a network in the cells. How PI 3-kinase lipid products interact with their target proteins. There is actually a whole family of PI 3-kinase enzymes that I will introduce you to, and then in the second part, I will focus on the role of PI 3-kinase in disease, cancer, overgrowth, and immune dysregulation. The first part of the basic science is quite technical, a lot of biochemistry there, but don't worry, we will repeat some of the concepts in subsequent slides. This is all pretty fixed and established at this point. The role of PI 3-kinase and disease and how drugs work is not entirely clear and here I will explain, give you my personal opinion on how some of the things are working or why they are not working.