Cellular Signalling 2

Question 1

Why are signal transduction pathways advantageous and what are they dependent on?

Answer 1

Amplifies the signal since each molecule involved can transmit the signal to numerous other molecules

More opportunities for control and coordination

Dependent on proteins interactions

Question 2

What are the steps to a phosphorylation cascade?

Answer 2

A relay molecule activates protein kinase I

Active protein kinase I transfers a P from ATP to inactive kinase 2 (activating it)

Active kinase 2 then catalyses the phosphorylation (and activation) of kinase 3

Active kinase 3 phosphorylates a protein (purple) that initiates cell response

Question 3

What are kinases and what is protein kinase?

Answer 3

Enzymes that phosphorylate molecules

Proteins kinases = enzyme that transfers phosphate groups from ATP to a protein

Question 4

What are secondary messengers? What is the primary signal messenger?

Answer 4

Small molecules (non-protein, water soluble molecules, or ions) that help relay the signal

Secondary messengers can diffuse throughout the cell - meaning they are readily available to the cell

The ligand is considered the primary signal messenger

Question 5

What is cAMP often made by and what are calcium ions’ role?

Answer 5

cAMP often made by the GPCR-activated adenylyl cyclase

Calcium ions can enter the cell through ligand gated ion channels and trigger cellular responses

Question 6

How does cAMP lead to a cellular response? (the steps)

Answer 6

First messenger binds to GPCR, activating it

Activated GPCR binds to G protein, which is then bound by GTP, activating the G protein

Activated G protein/GTP binds to adenyl cyclase. GTP is hydrolysed, activating adenyl cyclase

Activated adenyl cyclase converts ATP to cAMP

cAMP, a secondary messenger, activates another protein, leading to cellular response

Question 7

What is the compound widely used as treatment for erectile dysfunction?

Answer 7

cGMP

Question 8

How do calcium ions and IP3 activate proteins in a signalling pathway? What kind of messenger is calcium considered in this pathway?

Answer 8

A signalling molecule binds to a receptor leading to activation of phospholipase C

Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3

DAG functions as a secondary messenger in other pathways

IP3 diffuses through the cytosol and binds to an IP3 -gated Ca2+ channel in the ER, opening it

Ca2+ ions flow out of the ER, raising the concentration of cytosolic Ca2+

The Ca2+ ions activate the next protein in the one or more signalling pathways

**Calcium considered a third messenger because Ip3 acts before it

Question 9

Explain the breakdown of glycogen to yield glucose when the body is startled

Answer 9

Epinephrine is made in the brain and is sent out in the circulatory system (endocrine signalling)

Epinephrine receptors (a type of GPCR) in liver and skeletal muscle cells bind the circulating epinephrine

One response of these cells is the breakdown of glycogen into glucose so you can get away from the scary thing

Question 10

What is signal amplification?

Answer 10

What happens → at each step, many signalling molecules are activated, which in turn can activate many molecules of the next step and so on

Question 11

Why are signalling pathways important? What can they do?

Answer 11

Initiate gene expression (synthesises proteins)

Regulate metabolic pathways

Open ion channels

Regulate protein activity

Question 12

Explain what happens with a single pathway and a single response

Answer 12

A specific ligand can activate a specific receptor in one cell type to give response 1

Since different cells turn on different sets of genes, different kinds of cells have different proteins

Ex. liver vs heart cells

Question 13

Explain what happens when a branched pathway has multiple responses

Answer 13

A specific ligand can activate a specific receptor in a different cell type to give two different responses with two different phosphorylation cascades

Ex. one response could be regulation of enzyme activities, while the other could be transcription of specific genes

Question 14

Explain what happens when a crosstalk pathway has a single response

Answer 14

Two different ligands are activating two different receipts

The activation of one can either increase or inhibit the response of the other pathway - two different pathways interacting together
- This is called cross talk

Since difference cells turns on different sets of genes, different kinds of cells have different proteins
- Ex. liver vs heart cells

Question 15

Explain what happens when there’s a single pathway but different receptors - what’s an example of this?

Answer 15

Sometimes, in a completely different cell, the same ligand can activate a completely different receptor, which has different relay molecules and elicits a different response
- Ex. hormones

Question 16

How are scaffolding proteins used?

Answer 16

• Scaffolding protein are large relay proteins to which several other relay proteins are attached
• Used to help simplify the relay pathways
• These can permanently hold pathways and networks together to make for efficient design
  - Less distance to travel
  - Enhances speed and
  accuracy
  - Ex. brain signal transduction
  pathways are super complex
  but run very smoothly and
  quickly due to scaffolding
  proteins

Question 17

When termination of the signal transduction pathways reduces or stops the cell response, what happens to the different aspects of the reaction

Answer 17

Unbound receptors revert to their inactive forms

The GTPase activity of the G protein hydrolyses its bound GTP, converting it to GDP to turn off the G protein

cAMP is converted to AMP via phosphodiesterase

Proteins phosphatases inactivate phosphorylated kinases and other proteins