Lecture 11: Signal Transduction

Question 1

What are the types of cell signalling?

Answer 1

Paracrine, Autocrine, Endocrine

Question 2

What are the three stages of cell signalling?

Answer 2

1. Reception
2. Transduction
3. Response

Question 3

How is a signal detected (reception)?

Answer 3

When a ligand binds to a receptor protein on the surface of a cell or inside the cell

Question 4

What are thee types of receptors?

Answer 4

GPCR, Catalytic receptors, Ligand-gated ion channels, Nuclear receptors

Question 5

How do ligands transmit information to a cell?

Answer 5

By inducing a conformational change (change in shape) of the receptor

Question 6

What is transduction? Use the example of Adrenaline.

Answer 6

When an agonist induces a conformational change in the receptor it initiates the process of transduction.

1. The hormone activates the GPCR, which activates the G protein, why activate adenylate cyclase (membrane bound enzyme), which activates protein kinase A (second messenger), which activates a kinase which phosphorylates another kinase, and so on and so forth until the final kinase phosphorylates a specific protein causing a change in its activity.

Question 7

How does amplification work in transduction?

Answer 7

Kinases can phosphorylate multiple kinases!

Question 8

Where does the phosphorous come from?

Answer 8

The conversion of ATP to ADP

Question 9

In the response, GPCR activate different kind of secondary messengers. List some.

Answer 9

Cyclic AMP, diacylglygcerol, inositol triphosphate.

Question 10

What is the heterotrimeric G protein?

Answer 10

An inactive form of the G protein made up of three different proteins a,b,y

Question 11

What does the By and a group do?

Answer 11

By subgroup perform signalling roles

A subunit interacts with plasma membrane enzymes

Question 12

What are the three types of a subunits?

Answer 12

• Gαs – stimulates the production of cyclic AMP (cAMP)
• Gαi – inhibits the production of cAMP
• Gαq – increase diacylglycerol (DAG) and inositol triphosphate (IP3) production

Question 13

How does intracellular calcium increase?

Answer 13

The release of calcium from the ER by means of Gαq signalling

Process:

1. GPCR is stimulate by an agonist (e.g. oxytocin)
2. GPCR interacts with G-protein. The oxytocin activates the Gαq subunit (GDP disassociates and GTP attaches)
3. Gαq activates PLCB
4. PLCP cleaves PIP2 and DAG and IP3 activating PKC
5. IP3 then moves into the cytoplasm and interacts with a ligand gates ion channel on the ER, releasing calcium into the cytoplasm

Question 14

Where does calcium come from?

Answer 14

Stored in the ER and mitochondria.

Question 15

Muscular contractions is when actin fibres and pulled and slide past myosin fibres. What does this require?

Answer 15

ATP and Calcium

Process:

1. Intracellular Ca2+ increases
2. Ca2+ binds to and activates calmodulin, forming calcium calmodulin (CaCM)
3. CaCM then binds to and activates the myosin light chain kinase (MLCK).
4. This complex then catalyses the transfer of phosphate to myosin heads, activating myosin head ATPases

This then allows muscle contraction to occur:

1. Myosin cross bridge attaches to actin
2. Myosin head pulls on the actin filament and releases ADP and Pi
3. New ATP attaches to the myosin head as it detaches from the actin
4. ATP is split into ADP and Pi, cocking the myosin head.

Question 16

What causes the relaxation of muscles?

Answer 16

B2 and NO

Question 17

How can desensitization occur?

Answer 17

Change in receptors (phosphorylation), down regulation of receptors (internailization/reduced expression), depletion of mediators, increased metabolic breakdown