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Printable Handouts
Navigable Slide Index
- Introduction
- How it all started
- Cell signalling pathways is like a wiring diagram
- Protein phosphorylation / Protein kinase
- Mutations in protein kinases and human diseases
- Aims of work on signal transduction components
- Peutz Jeghers cancer syndrome
- LKB1 is a very simple protein kinase
- LKB1 pathway
- LKB1 is required for induced AMPK activation
- LKB1 pathway and cancer
- LKB1 pathway in regulating PTEN-tumourigenesis
- LKB1/AMPK signalling pathway inhibits mTOR
- Aim and approach of the study
- LKB1/AMPK effect on tumour development
- Analysis of LKB1 and PTEN in liver
- Inhibition of AMPK in LKB1 hypomorphic mice
- Incidence of tumours in LKB1/PTEN mice
- Conclusions (1)
- AMPK activators
- Treatment with AMPK-activators
- Activation of AMPK in mouse tissues
- Tumourigenesis in LKB1 fl/+ PTEN +/- mice
- AMPK activators fail to suppress growth
- AMPK activation fails to suppress mTOR activity
- Summary
- Does taking metformin protect from cancer (1)
- Does taking metformin protect from cancer (2)
- LKB1 exists in a complex in cells
- The LKB1:STRAD:MO25 complex
- 10% of all kinases are pseudokinases
- Potential evolution of a pseudokinase
- Structural analysis of LKB1:STRAD:MO25
- Expression and crystallisation of the complex
- LKB1:STRAD-alpha:MO25-alpha complex
- How is LKB1 activated by STRAD and MO25
- Location of LKB1 cancer mutations
- STRAD binds ATP in an active conformation
- Active protein kinases and their inhibitors
- How protein kinases become activated
- Ancestral mechanism to activate kinases
- Protein kinases evolution
- LKB1 activation of protein kinases
- Analysis of the NUAK protein kinase
- NUAK1 interacts with MYPT-PP1 complex
- Myosin phosphatase complex
- 3 conserved GILK motif on NUAK1/2
- NUAK binds to MYPT complex via PP1
- NUAK phosphorylates MYPT1 at 3 residues
- NUAK1 dependent phosphorylation of MYPT1
- Phosphorylation of MYPT1 by NUAK1 (1)
- Phosphorylation of MYPT1 by NUAK1 (2)
- NUAK1 phosphorylation affect on adherence
- NUAK1 knockout cells are more adherent
- Cell migration of NUAK knockout cells
- Effect of MYPT phosphorylation on its activity (1)
- Effect of MYPT phosphorylation on its activity (2)
- Pathway summary
- Conclusions (2)
Topics Covered
- Mutations in LKB1 kinase cause Peutz Jeghers cancer syndrome
- LKB1-activation and effects
- LKB1/AMPK signaling pathway inhibits mTOR
- Evaluating the role of LKB1 in regulating PTEN-induced tumourigenesis
- AMPK-activators-mechanisms of action
- AMPK-activators delay tumor onset in mice
- Metformin as a useful drug in cancer prevention
- The LKB1:STRAD:MO25 complex
- Potential evolution of a pseudokinase
- LKB activation by STRAD and MO25
- Location of LKB1 cancer mutations
- Activating protein kinases as a key challenge
- Analysis of the NUAK protein kinase
- Studying the role LKB1/NUAK1 signaling pathway in regulating cell adhesiveness and migration
- Modeling the novel LKB1
Links
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Talk Citation
Alessi, D. (2011, March 22). LKB1 pathway and its role in cancer [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 22, 2024, from https://doi.org/10.69645/RTNL2799.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Dario Alessi has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Cell Biology
Transcript
Please wait while the transcript is being prepared...
0:00
Hello I'm Dario Alessi,
working at the MRC Protein Phosphorylation Unit at University of Dundee.
And in this lecture, I'm going to tell you about the fascinating LKB1
signaling pathway and it's role in cancer.
0:16
So, I'm going to start by giving a short introduction in signal transduction
and why we are interested in this and what got us interested in LKB1.
So, at first glance,
the human body might only seem to be a bundle of tissues
and organs contained by blood vessels,
but for organisms to survive,
every cell must be able to function in harmony with
its neighbors and be able to sense its ever-changing environment.
Now, to accomplish this task,
each cell has developed an intricate web of molecular highways
which they use to communicate with each other and decide what goes on in the outside world.
Life scientists, such as myself,
refer to these channels of communication as the cell signaling pathways or networks.
And these pathways play essential roles in
controlling processes such as cell growth and proliferation,
but they also play much more basic roles,
for example, they control the cell's capacity to absorb and store nutrients
from the outside environment to be used as resources for fuels.
So, researchers first studied these signaling pathways out of interest,
but it's become a much greater urgency to
work on these signaling pathways since it's become
clear that defects in these pathways are the cause of many common diseases,
such as cancer, diabetes,
inflammatory diseases, and neurodegenerative diseases.
And that's what I'm going to tell you about in this talk.