PSC2002/L13 Broad Principles of Cell Signalling

Question 1

Give 3 key processes affected by cell signalling in the body.

Answer 1

Metabolism
Nervous system
Cell cycle
Immunology
Development
Physiology
Pharmacology

Question 2

What percentage of the genome of eukaryotic cells codes for signalling molecules?

Answer 2

10-15%

Question 3

Give 2 kinds of signals that cells are able to respond to.

Answer 3

Physical (light, heat, pressure)
Chemical

Question 4

What are the 4 stages of cell communication?

Answer 4

Secreting cell synthesis & release
Chemical signal
Target cell reception
Response

Question 5

Give 3 examples of cellular responses.

Answer 5

Secretion
Metabolism
Contraction
Cell growth
Excitability

Question 6

How do cells produce a response from the signal-receptor interaction?

Answer 6

Decoding reception -> response from target cell/tissue

Question 7

Give 3 methods of cell-cell communication.

Answer 7

Gap junctions
Autocrine & paracrine signals
Hormones
Neurotransmitter
Neurohormone

Question 8

Give the 5 kinds of signalling pathway.

Answer 8

Steroid hormone
Ligand-gated ion channel
Cyclic AMP pathway
Phosphoinositide pathway
Tyrosine kinase pathway

Question 9

Give the 8 steps in the signalling pathway.

Answer 9

Chemical signal
Receptor
Transducer
Amplifier
2nd messenger
Effectors
Response element
Response

Question 10

Give the 8 components in the cAMP to CFTR pathway.

Answer 10

Chemical signal - hormones
Receptor - G-protein-linked
Transducer - G-proteins
Amplifier - Adenylyl cyclase
2nd messenger - Cyclic AMP
Effectors - Protein kinases
Response element - Ion channels
Response - Secretion

Question 11

Give 4 basic principles of signal processing.

Answer 11

Amplification
Heterogeneity - diversity concept
Information transfer
Dynamics

Question 12

Describe amplification.

Answer 12

A single hormone-receptor interaction can be amplified by up to 10^6

Question 13

Describe heterogeneity.

Answer 13

Each pathway component often has multiple forms and cells can mix and match components
How different cells can respond differently to the same signals

Question 14

Describe information transfer.

Answer 14

Information is passed from one component to the next using two basic mechanisms

Question 15

Describe dynamics.

Answer 15

Responses are dependent on both temporal and spatial aspects of signalling components

Question 16

Describe amplification as it occurs in the cAMP signalling cascade. (5)

Answer 16

Signal molecules binds to GPLR
G protein turns on adenylyl cyclase (amplifier enzyme)
Adenylyl cyclase converts ATP->cAMP
cAMP activates protein kinase A
Protein kinase A phosphorylates other proteins, leading ultimately to cellular response

Question 17

Describe heterogeneity in G-protein linked receptors.

Answer 17

a subunit gives many different Ga responses
By subunit gives many different GBy responses

Question 18

Give an example of information transfer.

Answer 18

Chemical signal to receptor
Receptor to G-protein
G-protein to amplifier
2nd messenger to protein kinase

Question 19

Describe conformational changes in membrane-associated proteins. (4)

Answer 19

G-proteins transduce signals by binding to other proteins on plasma membrane
After short delay, turned off via GTP-hydrolysis by a subunit (molecular switches)
a subunit inactivated and dissociates from target protein
Inactive a subunit reassembles with By complex to reform inactive G protein

Question 20

Describe covalent modification.

Answer 20

Addition of terminal phosphate group of ATP to OH group of specific aa within target protein by PK
PK only phosphorylates residues that lie within specific PK ‘consensus motif’
Most common residues phosphorylated in mammalian cells are serine and threonine (tyrosine less)

Question 21

How does phosphorylation change a protein? How is it reversed?

Answer 21

Changes activity or function
Reversed by dephosphorylation of target residues by protein phosphatases

Question 22

How does cAMP pass information down the signalling pathway? (3)

Answer 22

Activates cAMP dependent protein kinase (PKA)
Causes conformational change
Release and activation of catalytic subunits

Question 23

Describe the difference between type I and II PKA.

Answer 23

Type II forms a stable interaction with AKAPs via R subunits
Not free in cytosol like type I
When cAMP binds to R subunits of Type II, catalytic subunits are NOT released (unlike type I)

Question 24

Describe temporal dynamics. (4)

Answer 24

Changes in abundance
Change in identity
Change in location
Change in dynamics
Can all affect response (decoding by cell to produce distinct downstream responses)

Question 25

Describe spatial dynamics in cardiac cells.

Answer 25

Stimulation of cardiac cells by noradrenaline leads to spatial differences in cAMP levels in different cell parts
Different agonists produce distinctive spatial responses which are decoded into different functional outputs from cells