Regulation Of Signalling Pathways

Question 1

Explain 2 ways how cells can respond to signals differently ?

Answer 1

1- use of different receptors

2- activating different intracellular machinery

Question 2

How is the use of nicotinic or muscarinic receptors an example of how cells respond differently

Answer 2

Nicotinic receptors when bound to AcH cause skeletal muscle contraction

Muscarinic G protein receptors cause hyperpolarisation instead (IPSP) and

Eg reduce heart rate in heart muscle

Question 3

Responses of cells needs many signalling pathways to interact. Explain 2 ways these can interact

Answer 3

Either molecules binding to different receptors can activate same protein to then transduce signal

Or can activate seperate proteins (phosphorylate) but then come togrther in same pathway

Question 4

How is activation of PKa when adrenaline binds and cyclic amp produced = example of signals combining

Answer 4

PKa activates phosphorylase B but inhibits glycogen synthase at the same time (to allow production of glycogen to glucose)

Question 5

What is it called when both AcH pathway and the pkA combine to activate phosphorylase kinase (glycogen into glucose) and how do they do it

Answer 5

Synergistic activation

PKa phosphorylates it

And ca2 released from AcH binding also activates it

Question 6

How is the overlap between pathways negative? Eg by using same signal molecule

Answer 6

There is risk of signal producing wrong responses

Question 7

Name the 3 signalling complexes that keep signals organised despite overlap

Answer 7

1- stabilising signalling complex

2 - transient signalling complex

3- transient by modification of phospholipids

Question 8

What is the stabilising signalling complex

Answer 8

Use of scaffold proteins attached to receptors and all signalling proteins together = keep them together

Question 9

What is transient signalling complex

Answer 9

Organising signal pathways by assembly of the proteins and receptor AFTER signal molecule binds

Question 10

What are the sites called that help organise signalling proteins in the transient signalling complex and what do they do

Answer 10

Phosphoinositide docking sites
(Phosphatidyl inositol phospholipids)
They phosphorylate when receptor bound to ligand

Allows activation of proteins which bind to them

Question 11

What do phosphoinositide docking sites do

Answer 11

Hold and activate / phosphorylate the signalling proteins (transient signalling complex)

Question 12

Name the 4 ways of switching signals off (stopping things like cell proliferation)

Answer 12

1- removal/inactivation of signal molecule

2- removal/ inactivation of receptor

3- inactivation of signalling proteins

4- degradation of secondary messengers (eg camp)

Question 13

What are the 3 ways or removing/ degrading signal molecules / explain them

Answer 13

1- degradation eg by enzyme (AcH esterase)

2 - recycling eg reuptake of NTs in synapse

3- SEQUESTRATION - hiding signal molecules in cleaved receptors eg in endosomes

Question 14

What is receptors mediated endocytosis (how is it an example of removing a receptor to stop signal)

Answer 14

Receptor travels into the endosome and then into a lysosome where it is degraded (permanently)

Question 15

Name the 3 ways of inactivating a signalling protein

Answer 15

Dephosphorylation/phosphorylation of the protein = switched off

2- GTP hydrolysis (in G proteins)

3- allosteric inactivation - dissociating the activated protein and the G protein to inactivate it

Question 16

How is cholera an example of how GTP hydrolysis is important to switch signal off

Answer 16

Adenylate cyclase stays bound to active G protein

Constant production of cAMP messenger = dehydration = death

Question 17

How does degradation of secondary messengers like cAMP and cGMP occur?

Answer 17

The circular phosphate on the adenosine mini phosphate is bound by phosphodiester bonds

Phosphodiesterase breaks these bonds forming 5’ AMP

Question 18

Give an example of a drug that prevents the degredation of cGMP into 5’GMP

Answer 18

Viagra. It does this so that cyclic gmp can fully relax muscles for longer

Question 19

Explain different intracellular machinery in pancreatic and endothelial cells

Answer 19

When both have activated phospholipase C which releases calcium and produces calcium calmodulin complex,

In pancreatic this activates protein kinase and this allows secretion of enzymes eg amylase

In endothelial the calmodulin complex activates NO synthase and NO is released

= muscle relaxation when bound to guanylyl receptors (GTP into cGMP)