Hormone receptors and signalling

Question 1

What is target cell specificity

Answer 1

target cells must have specific receptors to which hormone binds

Question 2

What 3 things influence target cell activation

Answer 2

[hormone]
number of receptors
affinity of receptors

Question 3

Receptor regulation What happens in chronic high/low hormones?

Answer 3

chronic high - cells dampen down signal to prevent over-activation -> decreased no receptors
chronic low - more receptors expressed

Question 4

what are the 4 superfamilies of receptors and explain each of them
from fastest to slowest

Answer 4

Ligand-gated ion channels
G-protein-coupled receptors
catalytic receptors
nuclear (intracellular) receptors

Question 5

What are the 2 types of hormones?

Answer 5

water soluble

lipid soluble

Question 6

G-protein coupled receptor:
What are the 3 subunits
At rest, where are they?
What enzyme does the alpha-subunit have?
What molecule is attached to the alpha sub-unit?

Answer 6

• alpha, beta, gamma
• GTPase
• GDP

Question 7

When a ligand binds, what happens to the alpha-subunit? To the GDP?

Answer 7

binding causes conformation change and allosteric change in G-alpha
exchange of GDP for GTP = activated G protein

Question 8

What happens to the G subunits after the GTP is added:

What do G-alpha-s, G-alpha,I, G-alpha-q/11, and G-beta-gamma do?

Answer 8

• G-alpha dissociates from beta-gamma. they in tern activate effector molecules

G-alpha-s - Stimulate adenylyl cyclase
G-alpha I - inhibit adenylyl cyclase
G-alpha-q/11 - stimulate phospholipase C
G-beta-gamma - multiple - activate K+, inhibit Ca2+ channels

Question 9

In detail what does the G-alpha-s do? What enzyme is affected at the end?
2 example hormones?

Answer 9

Affects ATP to convert cAMP through adenylyl cyclase
affects enzyme protein kinase A (PKA) to become active - e.g. glycogen breakdown
-glucagon
-adrenaline

Question 10

what does G-alpha-I do? 2 example hormones?

Answer 10

blocks adenylyl cyclase from changing cAMP

• somatostatin
• dopamine

Question 11

What does alpha-q do:
What enzyme affected first? Where is it?
What gets chopped up? 2 products?
What does each of the 2 products do?

Answer 11

phopholipase Cbeta

Converts PIP2 into DAG and IP3. DAG then activates PKC. IP3 then activates an IP3 receptor to release Ca2+

Question 12

What happens when the ligand is no longer bound to the G-protein coupled receptor:
Why is the GTP hydrolysed?

Answer 12

receptor reverts to resting state

GTP is hydrolysed to GDP (ATPase activity) and subunits re-assemble

Question 13

Give 2 example hormones for TK receptors
What do TK receptors do when a ligand binds?
What about in terms of phosphorylation?
What enzyme responsible?
What do adaptor proteins do?

Answer 13

• insulin
• IGF-1

-phosphorylates the target proteins

Tyrosine kinase
then adaptor proteins recognise the phosphorylated receptor
-produce multiple signal, incl gene expression changes

Question 14

Explain the full process of insulin receptor signalling (IRS)

Answer 14

IRS is then phosphorylated forming PI-3-kinase to PIP2 into PIP3
then phosphorylates further
activated insulin receptor is also recognised by Shc -> another cascade

Question 15

Give example hormones for nuclear receptors
Distinguish homo- and heterodimers
What is the main groups of nuclear receptors? Which is predominantly homo, and heterodimer?

Answer 15

Type I- steroid hormones (mainly cytosolic, homodimers)
Type II, non-steroid hormones (mainly nuclear, heterodimers with RXR)

homodimers means 2 receptors of the same working together as a pair, then heterodimer means 2 different receptors working together

retinoid X receptor

Question 16

What are type 1 nuclear receptors AKA?
Explain the mechanism of ligand bidnign to action
Example hormones?

Answer 16

steroid hormone receptors
Receptor is first a monomer, but the chaperones are bound to it. The chaperones bind to steroid receptor at rest. When steroid hormones bind to the receptor, it causes conformational change which leads to dissociation of the chaperone molecules, which then allows the dimer to form
Homodimer then goes into nucleus and influences gene expression

Question 17

What are type 2 nuclear receptors AKA?
Example hormones?
Explain mechanism of ligand binding to action

Answer 17

RXR and TR
all plasma membrane receptors
The thyroid hiormone receptor is unbound, but is bound to RXR as a heterodimer. There are also co-repressor molecules which suppresses gene expression
When T3 binds to the receptor, then co-repressors are booted out and co-activators are added in