14 - Phosphorylation Cascades Flashcards
What can an input into the cell lead to?
If you have an input in the cell (this input can be the activation of a transmembrane receptor e.g GCPR), it can lead to phosphorylation of a protein leading to conformational change
- and often in signalling mechanisms in the cell, it often requires two phosphorylation’s to activate an enzyme bringing in an extra safety step (in growth regulatory pathways)
What happens when there is as input in the cell?
Once this happens you have activation of an enzyme, often protein kinases, which phosphorylates another protein which is another kinase, which phosphorylates a third class of kinases, finally triggering an output event
o Often regulation of gene activity of transcription factors
o This is called the cascade of multistep phosphorylation (non-processive)
What does input from one receptor lead to?
Input from one receptor leads to the phosphorylation of many kinases
How many levels of control in signalling cascades?
Two levels of control: amplification of the signal and we don’t get activation of kinase III until kinase I and II due to the cascade
What was the first signalling cascade to be discovered?
The first cascade to be discovered was the ERK MAP cascade
What does receptor activation at the cell surface lead to?
Receptor activation at the cell surface leads to the activation of the MAPKKK which phosphorylates MAPKK which phosphorylates and activates MAPK- amplification at every step
What does MAPK phosphorylate?
MAPK phosphorylates a range of cellular proteins, for example other enzymes, protein kinases, and direct phosphorylation of transcription factors
What happens when the map kinase phosphorylates other protein kinases?
When the map kinase phosphorylates other protein kinases, these kinases themselves can phosphorylate even more protein kinases leading to the regulation of transcription factors, or the protein kinases can phosphorylate transcription factors, histones, ribosomal
What kind of phosphorylation does MAPK require?
Requires dual phosphorylation
o Serine/threonine phosphorylation
o And tyrosine phosphorylation
Give examples of MAP kinase pathways (model organisms)
o Roundworm: vulval development, humans: cancer (erkMAP kinase pathway) leads to tumour proliferation, and fruit flies: eye development
o These pathways start with a ligand which interacts with a receptor leading to the recruitment of an adaptor protein activating a GEF which regulates a G protein, which then leads to the MAPK cascade
With regards to MAPK, what leads to uncontrolled tumour formation?
In the ErkMAPK pathway there can be mutations in the EGRF receptor, the Ras protein and the Raf leading to uncontrolled tumour formation
