Topic 5 - Cell Signalling 2 Flashcards
Describe the speed and time course of contact-dependent signaling
Fast - less than a second to minutes
Describe the speed and timescale of signalling where molecules are relayed through the bloodstream
Slow - minutes to hours
Slow signalling typically involves altering…
Gene transcription
Fast signalling typically involves altering…
Specific proteins via phosphorylation, allosteric changes in ion channels, or actin rearrangements for example
Describe the difference between primary and secondary responses to a signal of a cell
Primary response: Signal induces transcription of a functional protein which acts to change cell behaviour
Secondary: Signal induces transcription of a transcription factor (protein 1) which then induces the production of a second protein which will exert effects causing a change in cell behaviour
What are 4 key ways in which cells are equipped to react to the same ligand (e.g. ACh) in different ways?
- Different receptors present
- Different intracellular signaling proteins present
- Different effector proteins present
- Different genes activated
In cells with the same intracellular machinery, how are they able to react to a signal in different ways?
Some ligands/factors are area-specific and create GRADIENTS, so the cell reacts to different concentrations of the molecule in different ways
Gradients of morphogens in animals are particularly important during…
Development
What are the 2 ways a morphogen can have a concentration gradient?
- Morphogen is area-specific
2. Morphogen is uniformly distributed but an antagonist for the morphogen is area-specific
Large intracellular signalling molecules can be… (kind of molecule)
Proteins exclusively (with very few exceptions)
What is the purpose of a scaffold protein?
Arranges proteins in a signal cascade in the correct order for succinct signalling
Integration of 2 signalling pathways requires a molecule which is activated by…
Coincidence detection
What is the purpose of anchoring in a signal pathway?
Anchors signalling molecules so the signal is localized
(1) and (2) are examples of modulators in a signal transduction pathway
Activators and inhibitors
Molecular switches have two conformations, which are…
Active and inactive
Monomeric GTPases are activated by…
GTP-binding induced by GEF
What are the 2 kinds of common molecular switches? (I.e. modes of “switching”)
Phosphorylation
GTP-hydrolysis
How many protein kinases are there in the human genome?
520
How many protein phosphatases are there in the human genome?
150
What is the difference between a phosphatase and a kinase?
Kinase = phosphorylates Phosphatase = removes phosphate groups
What are the 2 classes of molecules that signal using GTP binding?
Large trimeric g-proteins
Monomeric GTPases
What are 2 common kinds of kinases?
- Serine/threonine kinases
2. Tyrosine kinases
Scaffold proteins serve to minimize (1) and increase (2) of signalling pathways
- Cross talk
2. Specificity
What is the disadvantage of a pathway using a scaffold protein?
Not a lot of opportunity for amplification of the signal
Docking sites on a scaffold proteins are often created by…
Phosphorylating the scaffold
Describe how PIPs can be used as docking sites in signalling pathways
PIPs can be phosphorylated by receptors when they are activated, this attracts the binding of intracellular signalling proteins
What is a major purpose of a scaffold protein other than localizing things in the correct order?
Protein signals have to be in the right order but also in the right ORIENTATION, scaffolds maintain proper orientation so the proteins can interact
If a scaffold is modified to contain a flexible linker, what happens?
The scaffold is less effective, it is less able to orient signal molecules in the correct directions
Describe the response of a signalling pathway in which the curve of concentration:response is sigmoidal
After a certain threshold concentration of a molecule is reached, the response is amplified
Define desensitization
Prolonged exposure to a stimulus decreases a cell’s response to the stimulus