Positive and Negative Feedback Flashcards
1
Q
What is feedback
A
- Feedback is observed when the output from a given node follows a path of links that returns to regulate the node of origin.
- Distinct from negative and positive regulation – regulation is a result of the pathway activity
- How node can cause regulation upstream
2
Q
What is negative feedback
A
- Output inhibits its own production
3
Q
What if a cell is stimulated with a sustained input?
A
- In a normal, non adaptive response, output level increases with input and remains high during sustained input (the dynamic range of sensing is limited as the system reaches saturation).
- By contrast, in an adaptive system, output level is transient as input increases (the system automatically resets to basal steady state, even with sustained input).
4
Q
What does the process of adaption/desensitisation mean
A
- This process of adaption / desensitisation means that if the cell is stimulated with a sustained input:
- Initial burst of output
- Negative feedback occurs (after a short delay)
- Output levels return to basal level (resets)
- Even if the input stimulus remains at a high level
5
Q
How does responsiveness become reduced after an initial exposure?
A
- Reduce receptor number
2. Prevent coupling to intracellular signaling pathways (reduce effective receptor number):
6
Q
How can you reduce receptor number
A
- Endocytosis and sequestration of receptor in endosome
2. Destruction of receptor in lysosomes
7
Q
How can you reduce effective receptor number
A
- Inactivation (e.g. by phosphorylation)
- Inactivating downstream signaling
- Production of inhibitor protein that blocks the pathway
- (Typical of G-protein coupled receptor signalling for example)
8
Q
What is positive feedback
A
- Output stimulates its own production
9
Q
What happens when graded responses are cooperative
A
- Several cooperative modifications to become active
- Each event more likely than the last (increased affinity)
- Many signalling proteins are dependent on several cooperative modifications or binding events to become active.
- Cooperativity - each binding or modification event is made more likely than the last.
10
Q
What are allosteric proteins
A
- Allosteric proteins are proteins which have multiple-ligand binding site
11
Q
What are the 4 biochemical system types:
A
- Hyperbolic
- Ultrasensitive
- Bistable
- Oscillating
12
Q
What is a Hyperbolic system
A
- In a hyperbolic system, a response to an increasing stimulus is initially linear but then levels off as the system becomes saturated.
- Response increases as [ligand] increases
- Plateau is reached if protein kinase activation sites become saturated
13
Q
What is an ultrasensitive system
A
- Adds inhibitor to hyperbolic system
- Inhibitor: can bind reversibly to the ligand, inhibiting it
- An ultrasensitive system displays a sigmoidal dose-response curve because low levels of stimulus generate a poor response but higher levels generate an abrupt response.
- Response is dampened at low [ligand]
- Response rises abruptly when [ligand] ≥ [inhibitor]
14
Q
Describe a bistable system
A
- Once kinase is activated by binding to ligand it can phosphorylate and thereby activate a second kinase
- It can be a reversible phosphorylation
- Activated Kinase: can activate more K, without ligand
- Phosphatase: can inactivate activated K
- Low [ligand]: phosphatase inactivates protein kinase
- Increasing [ligand] doesn’t increase response much
- At threshold [ligand], protein kinase activity overpowers phosphatase activity, regardless of the [ligand] once is has begun.
- The signal continues without the initial stimulus (positive feedback)
- A bistable system is able to exist stably in one of two alternate states, but cannot come to rest in an intermediate state between them.
- This loop is self sustaining – if you remove input, the kinases would still remain active
15
Q
Give an example of bistability
A
- Many transcription factors, once activated, can associate with their own promoters and promote their own transcription.
- So for example, the initial input might activate TF1, which might drive the transcription of TF2, expression of TF2 might drive it’s own expression – this is really common.
