Session 7.1: Signal Transduction 1

Question 1

what is signal transduction

Answer 1

important for cells to respond to extracellular signalling molecules (eg: hormones, neurotransmitters, growth factors etc) and require receptors for this.

Question 2

what are the different types of receptors

Answer 2

intracellular - steroid and thyroid - can penetrate interior of cell
extracellular - plasma membrane is barrier so receptor at cell surface

Question 3

why is transduction required

Answer 3

some receptors able to directly alter cellular activity but many require transduction of initial ligand binding event via other intracellular signalling components to generate a response

Question 4

with what actions might transduction be required

Answer 4

contraction, secretion, proliferation, differentiation

Question 5

what are the 3 superfamilies of cell surface receptor and examples of these

Answer 5

G protein coupled receptor (7TM) - muscarinic acetylcholine receptor
ligand gated, receptor operated ion channels - nicotinic acetylcholine receptors
receptors with intrinsic enzymatic activity - receptor tyrosine kinase like insulin receptor

Question 6

what is a ligand

Answer 6

specific to a receptor

binding activates the receptor which brings about a change in cellular activity

Question 7

how is a receptor regulated

Answer 7

single endogenous agonist or other molecules that can be synthesised that bind with a high affinity to the receptor (exogneous)

Question 8

what are adrenoreceptors

Answer 8

9 G protein coupled receptors

Question 9

what are the key ligands that act at adrenoreceptors

Answer 9

1. adrenaline and noradrenaline - endogenous (activate all adrenoreceptors)
2. isoprenaline (only activate beta adrenoreceptors), salbutamol (only activates beta 2 adrenoreceptors), propranolol (antagonist - does not activate) - exogenous

Question 10

what are roles of g protein coupled receptors

Answer 10

in drugs that target GPCR’s
either act as agonists - bind and activate, transduction
eg: anti ashma - salbutmaol or analgesia - morphine
or act as antagonists - bind and not activate, prevent agonist acting
eg: CV hypertension - propanolol or neuroleptics - haloperidol

Question 11

how many GPCR’s are there in human genome

Answer 11

over 800

Question 12

what common structure do all GPCR’s share

Answer 12

single polypeptide chain (300-1200 amino acids) spans the membrane 7 time (7 transmembrane spanning region). the N terminal in extracellular space and C terminus intracellular/cytoplasm
= integral membrane protein

Question 13

what are the different types of GPCR’s and their roles

Answer 13

sensory GPCR’s sense light, odours and tastes

Question 14

different GPCR subtypes respond to different ligands, what are examples of these ligands

Answer 14

• ions (H+, Ca2+)
• neurotransmitters (acetylcholine, gluatamate)
• peptide and non-peptide hormones (glucagon, adrenaline)
• large glycoproteins (thyroid stimulating hormone)

Question 15

what are the two possible ways ligand binding sites can be formed for receptors - so where ligands bind

Answer 15

1. 2-3 of transmembrane domains

2. N terminus region/other extracellular domains

Question 16

how do GPCRs respond to ligands

Answer 16

changing their 3D conformation shape

allows agonist bound GDCR to bind to a second protein - G protein to facilitate the activation of the protein

Question 17

what does g protein stand for

Answer 17

guanine nucleotide binding protein

Question 18

what are the guanine nucleotide

Answer 18

G proteins bind GTP or GDP. able to hydrolyse GTP to GDP

Question 19

what is the structure of beta2-adrenoreceptor

Answer 19

heterotrimeric G protein
alpha subunit
beta subunit
gamma subunit