Signalling 1

Question 1

How is signal transduction specific?

Answer 1

1. Horomone released into local area
2. Each cell expressed specific group of receptors - different receptors can bind same horomone but stimulate production of different secondary messengers
3. Secondary messenger has specific effects
4. Cells express different isoforms of effectors

Question 2

How is signal transduction sensitive?

Answer 2

Hormone receptors have high affinity for their hormone so only low concentrations needed.
-> Enzyme catalysing formation of secondary messenger is a point of amplification
-> Some effectors stimulated, some inhibited + so enzymes favouring one pathway are activated while the opposing pathway is shut down
=> metabolism is turned around

Question 3

Outline receptor desensitisation

Answer 3

1. Enzyme shuts down signal when hormone not present
2. Enzyme breaks down 2nd messenger
3. Enzyme acts in opposition to 2nd messenger action
4. Pathway is no longer stimulated, despite presence of hormone

Question 4

How do signalling pathways integrate?

Answer 4

1. Cells express multiple hormone receptors on cell surface + can be exposed to many different hormones simultaneously
2. Each diff. receptor can bind its respective hormone at same time as other receptors
3. Different receptors may modulate concentrations of same sex. messengers
4. Different signalling pathways may alter same effectors

Question 5

Receptor: Hormone allosteric effects

Answer 5

Cytosolic domain

Question 6

Ca++ calmodium allosteric effects

Answer 6

Exposes hydrophobic areas that allow calmodium to interact with other proteins

Question 7

cAMP:PKA(R) allosteric effects

Answer 7

Regulatory subunits dissociate activating catalytic subunits

Question 8

Enzyme that acts opposite to Phosphatase and requirements

Answer 8

Kinase , ATP

Question 9

What bonds can phosphoryl group form?

Answer 9

H bonds

Question 10

Why do kinase act as amplification points?

Answer 10

Each kinase can phosphorylate multiple target proteins

Question 11

Protein domains are

Answer 11

reoccuring with high affinity for certain types of sequences

Question 12

Phosphotyrosine binding domain and SH2 similarities

Answer 12

Tyr- P

Question 13

SH3 binding domain consists of

Answer 13

3 prolines

Question 14

PH binding domain consists of

Answer 14

P-Inositol -P P

Question 15

EF-hand binding domain consists of

Answer 15

Ca++

Question 16

A paracrine hormone

Answer 16

Acts on nearby cells

Question 17

Prostaglandins belong in what class of hormone?

Answer 17

Eicosanoids

Question 18

Which GPCR loop interacts with G proteins?

Answer 18

3/4 or 5/6

Question 19

How many isoforms of Ga, Gb and Gy

Answer 19

20, 5, 6

Question 20

Gt classification

Answer 20

Activates retinal cyclic GMP phosphodiesterase

Question 21

Outline Gs stimulation by adrenaline

Answer 21

1. Gsa activation, GDP -> GTP
2. Gsa dissociation from b and y -> activates AC
3. ATP -> cAMP
4. cAMP activation of PKA by 4x attachment to R sub-units
5. R sub-units dissociate from catalytic sub-units
6. Target protein phosphorylated by PKA

Question 22

PKA characteristics

Answer 22

R2C2 heterotetramer: serine/ threonine kinase

• phosphorylates several enzymes
• > lipase, aCoA carboxylase, glycogen synthase, TF CREB +

Question 23

PKA consensus sequence

Answer 23

Arg, Arg, X, Ser/Thr, Z

Question 24

PKA sub-unit regulatory sequence

Answer 24

Arg, Arg, Gly, Ala, Ile

Question 25

Adrenaline: Gs points of amplification

Answer 25

1. Adrenaline: receptor complex catalyses GDP:GTP on multiple G-proteins -> each Ga binds to 1 AC 2. Each AC can catalyse formation of many cAMP - > 4 cAMP per 2x PKA 3. Each active PKA can phosphorylate many proteins

Question 26

Shutting down of Adrenaline: receptor complex

Answer 26

1. Adrenaline no longer present GTP -> GDP 2. GDP + a -> a + by subunits 3. AC no longer active 4. Remaining cAMP converted to AMP by cyclic nucleotide PDE 5. R-subunits no longer occupied by cAMP so reform with catalytic subunits 6. Phosphatases dephosphorylate proteins

Question 27

How do arrestins mediate desensitisation?

Answer 27

1. Block cytoplasmic face of receptor which prevents G-protein binding + activation 2. Arrestin links receptor to clathrin + AP2 -> endosome to form lysosome or recycled

Question 28

How does beta ARK mediate desensitisation?

Answer 28

βARK,a serine/threonine kinase, will phosphorylate serine and threonine residues on the β-adrenergic receptor. -> This will facilitate Beta-arrestin's binding to the receptor. Additional stimulation by epinephrine will now be unable to activate Gs due to arrestin.

Question 29

How is beta ARK an example of negative feedback?

Answer 29

It's activated by phosportylation of serine/ threoinine residues from PKA -> prevents overstimulation of of b-adrenergic receptor