+ and - feedback

Question 1

feedback is distinct from..?

Answer 1

regulation

Question 2

• ve feedback

- AKA

Answer 2

desensitisation / adaptation

Question 3

what happens if a cell is stimulated with a sustained input?

Answer 3

nonadaptive response

adaptive response

Question 4

nonadaptive response

Answer 4

increase in output

• > then plateaus
• > need higher level of input to increase output again

Question 5

adaptive response

Answer 5

initial burst of output
-> -ve feedback
–> output levels return to basal
(even if stimulus remains high)

Question 6

how does responsiveness become reduced after an initial exposure?

Answer 6

reduce receptor no.

block coupling to intracellular signalling pathway

Question 7

reducing receptor no.

Answer 7

receptor sequestration in endosome

receptor destruction via lysosomes

Question 8

blocks to intracellular signalling pathways

Answer 8

receptor inactivation
e.g. phosphorylation

inactivating intracellular signalling protein
-> prevents downstream signalling

produce inhibitory protein
- blocks pathway

Question 9

+ feedback

- generates…

Answer 9

all or nothing response

Question 10

allosteric proteins

- what do they need

Answer 10

have multiple ligand binding sites

need several cooperative modifications or binding events to be activated

each event increases input binding affinity

Question 11

allosteric proteins

- low vs high ligand concs

Answer 11

low = less response

more binding events
-> steeper response curve

Question 12

4 biochemical signalling system types

Answer 12

hyperbolic
ultrasensitive
bistable
oscillating

Question 13

hyperbolic system

• stimulus
• response

Answer 13

ligand conc
- can bind reversibly to a kinase

protein kinase activity

Question 14

hyperbolic system

- stimulus vs response graph

Answer 14

response increases as [ligand] increases
- initially linear

plateaus as kinases become saturated

Question 15

ultrasensitive system

- what is it?

Answer 15

add a ligand inhibitor

• > reversibly sequesters ligand
• > less ligand to bind to kinase

Question 16

ultrasensitive system

- response curve

Answer 16

sigmoidal shape

low levels of stimulus
-> poor response

when [ligand] > [inhibitor]
-> dramatic increase

high [ligand]
-> plateaus as all kinases saturated

Question 17

bistable system

Answer 17

node in pathway activated

• > can up regulate own activation + phosphorylate other proteins
  e. g. activate inactive kinase in absence of ligand

reversible
- ligand unbinds OR phosphatase remove activating P group

Question 18

bistable system

- +ve feedback

Answer 18

once kinases phosphorylated + activated

-> can further phosphorylate kinases

Question 19

bistable system

- response graph

Answer 19

all or nothing response

low [ligand]
- phosphatase inactivates kinase

increasing [ligand]
- response doesn’t increase much

threshold [conc]
- kinase activity > phosphatase activity
regardless of [ligand]

signal continues w/out initial stimulus

Question 20

bistability

Answer 20

ability to exist in 2 distinct stable output states

w/out a stable intermediate steady state

Question 21

2 examples of bistability

Answer 21

kinases

TFs

Question 22

bistability example

- kinases

Answer 22

input phosphorylates + activates kinase 1

• > kinase 1 phosphorylates + activates kinase 2
• > response

kinase 2 also phosphorylates kinase 1
= self-sustaining loop
-> dramatic response curve

Question 23

bistability example

- TF

Answer 23

activated

• > associate w/ own promoters
• > promote own transcription

input activates TF1
-> drives TF2 transcription
-> TF2 drives own transcription
= self-sustaining loop

Question 24

self-sustaining loop

Answer 24

if remove input

-> kinases/TFs would remain active

Question 25

hysteresis

Answer 25

= delay or lagging behind

- state of a system depends on its history + starting conditions

Question 26

bistable switch

= extreme form of hysteresis

Answer 26

input reaches threshold
-> output

when input reduced to original level
-> output not diminished
= self-sustaining system

Question 27

importance of + and - feedback

Answer 27

results in naturally oscillating cycling system

Question 28

oscillating system

Answer 28

same as bistable system

BUT
active kinase phosphorylates + activates an inhibitor

inhibitor can repress the 2 kinases in the system

Question 29

what is meant by oscillations?

Answer 29

output levels fluctuate between states of high + low activity in periodic manner

e.g. cell cycle

Question 30

-ve feedback with small delay causes..?

how do you introduce a delay?

Answer 30

damped oscillations

add more components to pathway
-> takes longer for -ve feedback to initiate

Question 31

-ve feedback with increased delay causes…?

Answer 31

more stable oscillations

- not damped

Question 32

oscillating system

- response curve

Answer 32

low [ligand]
- phosphatase inactivates K

threshold [ligand]
- K activity > phosphatase activity
-> K induces more + more activated K via + feedback
(regardless of [ligand]

after delay, phosphatase activate inhibitor
-> represses K activity via -ve feedback
until low enough to be ligand-dependent again

Question 33

+ve feedback systems

- how do they affect mitosis?

Answer 33

ensures all or nothing response
- cell starts mitosis or doesn’t

signal can continue w/out initial stimulus
- once cell starts mitosis, it will finish it

Question 34

-ve feedback systems

Answer 34

can produce a repeating oscillator

Question 35

oscillation works well if…:

Answer 35

there’s a delay before -ve feedback

activating signal is bistable (+ve feedback)