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Intracellular signalling Flashcards

1
Q

What is signal transduction

A

Converting 1st messenger to cellular function

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2
Q

What are the stages of intracellular signalling

A
  • reception
  • signal transduction
  • cellular response
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3
Q

What is the hierarchy in intracellular Signalling

A
  • 1st messenger
  • receptor
  • G-protein
  • effector enzyme
  • 2nd messenger
  • protein kinase
  • target protein
  • cell response
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4
Q

What is amplification

A
  • 1st messenger —> large response
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5
Q

What is cross-talk in specificity

A
  • 1st messenger stimulating diff. responses in diff cells
  • 1st messenger bind to diff receptors on same cell
  • 1st messenger stimulate different pathway
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6
Q

Example of specificity

A
  • adrenaline
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7
Q

Why is there complexity in signal transduction

A
  • 1000+ GPCRs
  • 500+ protein kinases
  • cross-talk
  • cell-type specificity
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8
Q

What are G-proteins

A
  • guanine nucleotide binding proteins
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9
Q

What is GTP

A

Guanosine trisphosphate

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10
Q

What is GDP

A

Guanosine diphosphate

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11
Q

What is the function of GTP

A
  • high energy

- activate G-protein

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12
Q

What do G-proteins do as GTPases

What do ligand-receptors do

A

Hydrolyse GTP —> GDP
Energy released
Opposite to GTPases

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13
Q

What is the process of receptor associated G-proteins

A
  • ligand binding —> GDP/GTP exchange
  • effector activation —> 2nd messenger
  • hydrolysis of GTP —> GDP
  • re-association of G protein subunits
  • loss of 2nd messenger
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14
Q

What is the effector enzyme and 2nd messenger of the following G-proteins:

  • Gas
  • Gai
  • Gag
A
  • adenylate cyclase (stimulation), cAMP
  • adenylate cyclase (inhibition), cAMP
  • phospholipase C (stimulation), DAG
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15
Q

What is the mechanism of cholera toxin (Gs)

A
  • inhibits GTPase activity
  • GTP remains “on”
  • over-stimulation of adenylate cyclase
  • accumulation of cAMP
  • loss of Cl-
  • osmotic gradient
  • water loss
  • dehydration
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16
Q

What are the syndrome of whooping cough

A
  • paroxysmal cough

- whooping

17
Q

What is the prevalence of whooping cough

A
  • 40-50m cases/y

- >250000 death/y

18
Q

What is the cause of whooping cough

A
  • bordetella pertussis
  • airborne respiratory droplet
  • virulent factor: pertussis toxin
19
Q

What is the treatment & prevention of whooping cough

A
  • antibiotics

- vaccination

20
Q

What is the mechanism of pertussis toxin (Gi)

A
  • prevents GDP/GTP exchange by Gi
  • “off” position
  • accumulation of cAMP
  • insulin secretion
  • increased sensitivity to histamines
21
Q

What is a 2nd messenger

A
  • short-acting intracellular molecule
  • rapidly formed/ released
  • result of receptor activation
22
Q

What are the 5 most common 2nd messengers

A
  • cyclic AMP, cAMP
  • cyclic GMP, cGMP
  • diacylglycerol, DAG
  • inositol 1,4,5-trisphosphate, IP3
  • intracellular calcium, Ca2+
23
Q

What is the production of cGMP catalysed by

A
  • guanylate cyclase

- activated by NO

24
Q

What enzyme breaks down cGMP

A
  • PDE

- GMP formed

25
The activation of which G-protein causes the production of DAG, IP3 and Ca2+
Gq
26
Give examples of receptors activating Gq pathway
- angiotensin ii on AT1 receptor | - adrenaline on alpha 1-adrenegeric receptor
27
What is the mechanism for Gq activation
- ligand-binding —> GDP/GTP exchange - effector enzyme activated —> 2nd messenger produced - IP3 released in cytosol —> Ca2+ released - DAG remains in memb. —> kinase C activated
28
What binds to ER to trigger Ca2+ release
- IP3
29
What are protein kinases
- enzymes facilitate transfer of P from ATP to specific aa (Ser, Thr, Tyr) in specific protein
30
What are the 3 main kinases groups
Serine/threonine Tyrosine kinases Dual-specificity (MAP -->MKKs)
31
How can kinases modulate protein function
- phosphorylation —> conformational change in protein | - phosphorylation of transcription factor
32
Check out slide 63 on lecture
Also check revision tip at bottom
33
What diseases are kinases inhibitors used to treat
- cancer - cardiovascular disease - HIV - AD
34
What are G proteins
- heterotrimeric | - Gas, Gai, Gay
35
What are small GTPases
- monomeric | - Ras, Rho
36
Which two G-proteins have the opposite effect on cAMP
Gs, Gi
37
what is the production of cAMP catalysed by
Adenylate cyclase
38
what is the production of cGMP catalysed by
Guanylate cyclase
39
what do PDEs do
- break down cAMP, cGMP | - inhibit caffeine & viagra

IMS (18 decks)

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