Cell signalling - G protein-coupled and Enzyme-Linked Receptor Signalling

Question 1

what are all physiological signals mediated through?

Answer 1

proteins

Question 2

what are proteins that are receiving signals termed as?

Answer 2

receptors

Question 3

what is signal transduction?

Answer 3

signals are converted to a cellular response

Question 4

cell signalling is?

Answer 4

specific and sensitive

Question 5

what does it mean when we say cell signalling is sensitive?

Answer 5

receptors detect conc of 10 -6 - 10 -9 molar

Question 6

what do we mean when we say cell signalling is specific?

Answer 6

precise binding between the signal molecule and the receptor - lock and key theory

Question 7

what states can receptors be in?

Answer 7

either an active state or an inactive state dependent on their conformation (shape)

Question 8

what are ligand-gated ion channels involved in?

Answer 8

in homeostasis, fast synaptic events, muscle contraction

Question 9

what happens when the ligand binds to the receptor?

Answer 9

conformational change allows transit of ions across the membrane

Question 10

how fast does the ion channel open for ligand-gated ion channels?

Answer 10

opens in milliseconds

Question 11

which processes are not involved in ligand-gated ions channels?

Answer 11

no intermediate biochemical processes are involved

Question 12

ionotropic receptors?

Answer 12

ligand-gated ion channels

Question 13

metabotropic?

Answer 13

protein-coupled receptors

Question 14

GPCR receptor structure?

Answer 14

7 membrane-spanning alpha helices

Question 15

What are GPCRs associated with?

Answer 15

signalling for wide range of processes: coding for more than 800 GPCRs identified
e.g. olfactionm regulation of immune responses and inflammation, homeostasis, autonomic nervous system neurotransmission, growth & metastasis of tumours

Question 16

G protein - how many parts and what are they called?

Answer 16

3 parts - alpha, beta and gamma

Question 17

GTP causes?

Answer 17

G protein to split in two –> alpha GTP part and the beta gamma part

Question 18

what causes the biological effect?

Answer 18

the GTP/alpha part of the G protein binding to the enzyme/ion channel

Question 19

slide 12

Question 20

slide 13

Question 21

how many main classes of G-protein are there and what are they?

Answer 21

4 main classes - they are
Gαs, Gαi, Gαq, Gα12/13

Question 22

What do Gαs and Gαi do?

Answer 22

they produce stimulation and inhibition of adenylyl cyclase which produces cyclic AMP.

Question 23

What is cyclic AMP?

Answer 23

cAMP is a secondary messenger that activates enzymes involved in many processes including energy metabolism, cell division and differentiation, ion transport, ion channels and contractile proteins in smooth muscle

Question 24

slide 16

Question 25

What are enzyme-linked receptors activated by?

Answer 25

a wide variety of mediators: growth factors, cytokines and hormones

Question 26

what do enzyme-linked receptors have a major role in?

Answer 26

major role in growth & cell division, inflammation, immune responses

Question 27

What are the main types of enzyme-linked receptors?

Answer 27

receptor tyrosine kinases (RTKs), receptor serine/threonine kinases and cytokine receptors

Question 28

what is the time course of effect for enzyme-linked receptors?

Answer 28

mintues-hours

Question 29

slide 23

Question 30

What is the first stage of kinase-linked receptor activation and inactivation?

Answer 30

ligand binds to receptors and this leads to dimerization

Question 31

What is the second stage of kinase-linked receptor activation and inactivation?

Answer 31

The association between the 2 intracellular domains creates an active kinase enzyme

Question 32

dimerization?

Answer 32

two ‘walls’ of channel come together

Question 33

What is the third stage of kinase-linked receptor activation and inactivation?

Answer 33

Tyrosine residues are phosphorylated

Question 34

What is the fourth stage of kinase-linked receptor activation and inactivation?

Answer 34

The phosphorylated tyrosine residues act as docking sites for other intracellular relay proteins (often enzymes) which are then themselves activated

Question 35

What is the fifth stage of kinase-linked receptor activation and inactivation?

Answer 35

A cascade of events ultimately leads to biological effect

Question 36

What is the sixth stage of kinase-linked receptor activation and inactivation?

Answer 36

The activity of the receptor is terminated by protein tyrosine phosphatases

Question 37

apoquel?

Answer 37

comes along and binds to binding site on receptros - causes dimerisation ofmtwo receptors molecules which axtivates the kinase enzyme - add phosphates groups itself- atrracts other enzymes currently inactive inside cell - take phosphate group and goes off to activate another enzyme and another and another etc - creates biological effect
Process continues as long as drug is attached - when it comes off the whole system is shut down

Question 38

heroin?

Answer 38

dimorphine