Cell signalling last slides Flashcards
(17 cards)
What are molecular switches
Can be turned off or on
Main examples include:
GTP binding
Protein kinases
What does GTPase-activating proteins do
hydrolyse gtp to gdp (inactivation)
What does guanine nucleotide exchange factors (GNEF) do
stimulates release of gdp and binding of gtp
What does nucloeitde-dissociation inhibitors do
Inhibits GTP binding
Which family consists of various monomeric GTPases
Ras family
Ras and Rho families relay signals from cell surface receptors
How does Ras signalling work
Ligand Binding:
When a ligand (such as a growth factor) binds to a cell surface receptor (like a RTK — receptor tyrosine kinase), it triggers a signaling cascade.
Ras-GEF Activation:
Ras-GEF (Guanine nucleotide Exchange Factor for Ras) is activated by the receptor.
Ras-GEF stimulates the dissociation of GDP from Ras, allowing GTP to bind.
Ras Activation:
When Ras binds to GTP, it becomes active and can initiate downstream signaling events.
Ras activates Raf, which is a kinase, and Raf begins a cascade of phosphorylation events that lead to various cellular responses (e.g., cell division, survival, differentiation).
Phosphorylation and dephosphorylation are mediated by which 2 enzymes
kinases and phosphatases
What do kinases do
add phosphates to target proteins by turning them on.
Phosphorylation can happen at Tyrosine, Serine and
Threonine residues.
o Kinases recognise specific amino acid sequences
around the phosphorylation site in target proteins
What do phosphates do
Remove phosphates turning proteins off leading to dephosphorylation
What is an example of receptor tyrosine kinase
Epidermal growth factor receptor
These phosphorylaes and activate themselves (example of receptors with intrinsic enzymatic activity)
How do receptor tyrosine kinases lead to response
Signal protein binds to the ligand binding domain on the extracellular
side of the receptor
2. Activating the tyrosine kinase domain on the cytosolic side
3. Leads to phosphorylation of the tyrosine side chains.
4. This creates phosphotyrosine docking sites for various intracellular
signalling proteins that relay the signal downstream
How does the cell ensure specificity of signal transmission?
By using scaffold proteins
which brings together a group of interacting signalling proteins.
The a scaffold holds the proteins in
close proximity enabling them to
interact and be sequentially activated.
Other than scaffold, how else does the cell ensure the specificity of a signal?
Via signalling complexes.
fter a receptor is activated by its ligand, it becomes phosphorylated on its intracellular tail, which creates binding sites for signaling proteins.
These proteins then assemble at the receptor, forming a signaling complex.
Once the signaling proteins are in place, they are sequentially activated in a cascade, propagating the signal through the cell and leading to a cellular response.
Phosphoionositide docking site
Receptor activation on the plasma membrane leads to the production of modified phosphoinositides (like IP3 and DAG).
These modified phosphoinositides act as recruitment sites for intracellular signaling proteins that have binding domains specific for phosphoinositides.
The binding of these proteins to the phosphoinositides activates them, and they can then carry out their signaling functions, such as activating other proteins or initiating further signaling pathways.
This process helps organize the signaling response and ensures it occurs efficiently at the right location in the cell.
Interaction domains
Interaction domains are specific parts of proteins that are good at recognizing and binding to other proteins or molecules
Domains bind to what?
either an amino acid sequence, covalent modification (eg. Phosphorylation), or
protein domain
Cells can adapt to external stimuli through sensitivity adjustment. What are the 3 methods in which they do this
1.Reduced surface expression of the receptor
* Receptor internalisation (and possible
degradation)
2.Receptor inactivation
3.Inactivation of the downstream signalling
* Inactivation of activatory signalling proteins
* Activation of inhibitory signalling proteins
