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Printable Handouts
Navigable Slide Index
- Introduction
- PI 3-kinase (PI3K)
- Overview
- PI lipids in cell membranes
- PI3Ks basic function
- Inositol lipids are built around the Phosphatidyl-Inositol (PI) building block
- PI3Ks: phosphorylate the 3 position of phosphatidyl-inositol lipids
- 3-PI ≠ IP3
- The PI lipid network
- The PI-network is key in cell biology & signalling
- PI3K lipids & their target proteins
- Mammalian cells contain four distinct 3-phosphoinositides
- Different PI3K lipids have different binding partners
- Class I PI3K lipids bind to PH domains found in a diverse set of molecules
- Akt/PKB Ser/Thr kinase as an example of a PI3K effector cascade
- PI3K enzyme family
- PI3K: a family of enzymes
- Signalling by class I PI3K isoforms
- Class I PI3K signalling
- Take-home messages (1)
- PI3K in disease
- PI3K signalling
- PI3K signalling is often hyperactivated in cancer (1)
- PI3K signalling is often hyperactivated in cancer (2)
- PI3K signalling is often hyperactivated in cancer (3)
- Low dose of PI3Kα inhibitor is effective in PROS
- PI3K isoforms & approved PI3K inhibitors (1)
- PI3Kα-targeted therapy for cancer: ‘smart’ combination therapy
- PI3K isoforms & approved PI3K inhibitors (2)
- PI3Kδ
- How do PI3Kδ inhibitors work? I. B-cell malignancies (1)
- How do PI3Kδ inhibitors work? I. B-cell malignancies (2)
- How do PI3Kδ inhibitors work? I. B-cell malignancies (3)
- How do PI3Kδ inhibitors work? II. In haem & solid tumours (T cells) (1)
- How do PI3Kδ inhibitors work? II. In haem & solid tumours (T cells) (2)
- Can PI3Kδ and PI3Kγ inhibitors be used to treat solid tumours?
- The changing landscape of PI3K inhibition in cancer – a summary
- Take-home messages (2)
- Thank you!
Topics Covered
- Phosphoinositide lipids and their metabolism
- Lipid second messengers produced by PI 3-kinases (PI3Ks)
- PI3K lipids transduce signals via binding to lipid-binding modules in proteins
- Multiple PI3K isoforms with specific biological functions in mammals
- Aberrant PI3K activation in cancer, overgrowth and immunity
- Clinical trials with PI3K pathway inhibitors
- Approval and Challenges for PI3K inhibitors in cancer treatment
Links
Series:
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Talk Citation
Vanhaesebroeck, B. (2020, August 31). PI 3-kinases and lipid messengers [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 23, 2024, from https://doi.org/10.69645/SZWD7686.Export Citation (RIS)
Publication History
Financial Disclosures
- Bart Vanhaesebroeck is currently an advisor to Venthera (Palo Alto, US), iOnctura (Geneva, Switzerland) and Karus Therapeutics (Oxford, UK), and has been an advisor to Retroscreen (now hVIVO/Open Orphan), Activiomics (London, UK - Co-Founder); Glaxo SmithKline (Stevenage, UK), Intellikine, (San Diego, US); AstraZeneca (Sweden); PIramed (Slough, UK) and Serono (Geneva, Switzerland), and has received speakers fees from Gilead (Foster City, US) and Novartis (Basel, Switzerland). Prof. Vanhaesebroeck has also received academic, non-commercial grants from Cancer Research UK.
A selection of talks on Biochemistry
Transcript
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0:00
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.
0:20
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.
1:23
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.