Lecture 14: Receptors 2

Question 1

What is a second messenger? Give five examples of these:

Answer 1

These are intracellular molecules that change in concentration in response to receptor activation and transmit signals from the receptor to other relay molecules because they are not attached to the membrane.

Examples:
cAMP
cGMP
Calcium ions (Ca2+)
IP3
DAG

Question 2

Do different receptor types use the same signal transduction processes?

Answer 2

No, different receptor types typically use distinct signal transduction processes.

GPCRs: Use G-proteins and second messengers like cAMP.

RTKs: Involve autophosphorylation and kinase cascades.

Ion Channels: Allow ion flow, altering membrane potential.

Nuclear Receptors: Directly regulate gene expression.

While pathways can interact (cross-talk), each receptor type has a unique signaling mechanism.

Question 3

How is phosphorylation and dephosphorylation important in signal transduction pathways?

Answer 3

Phosphorylation: Protein kinases transfer phosphates from ATP to proteins, activating or altering their function.

Dephosphorylation: Protein phosphatases remove phosphates, turning off or modulating protein activity.

These events create a phosphorylation cascade, allowing for precise control and amplification of signals within the pathway.

Question 4

Give a reason why ligand-gated ion channels provide faster signaling than GPCRs and RTKs:

Answer 4

An agonist ligand that binds causes a conformational change to activate the receptor

Instead of “relay” proteins like G proteins or adaptors being used, ions directly flow through the channel to produce effects. Thus provide faster signaling than GPCRs or RTKs

Question 5

Explain how the same receptors on different cell types mediates different responses.

Answer 5

The same ligand/receptor pairing can have different effects in different cells because they use different combinations of relay molecules for signal transduction.

Question 6

Outline the signal transduction mechanism for the insulin receptor in muscle/adipose tissue:

Answer 6

Insulin binds to its receptor (a receptor tyrosine kinase), triggering phosphorylation of an adaptor protein and further signal transduction events

This process promotes glucose uptake by translocating GLUT4 transporters to the cell membrane (via exocytosis), allowing glucose into the cell.

Question 7

What role does Ga (s) and Ga (i) play on GPCRs?

Answer 7

Ga (s) is a stimulatory G protein (agonist ligand for GPCRs), which activates an enzyme called adenylate cyclase

Ga (i) is a inhibitory G protein (antagonist ligand for GPCRs), decreases the activity of adenylate cyclase

Question 8

What are some examples of peptide ligands?

Answer 8

• Insulin (produced in pancreatic B-Cells)
• GLP-1 (produced in the gut and acts on Pancreatic B-cells)
• Glucagon (produced in pancreatic A-cells)

Question 9

What is the signal transduction mechanism of the insulin receptor in liver cells?

Answer 9

In liver cells, insulin binds to its receptor (a receptor tyrosine kinase), causing phosphorylation of an adaptor protein, and further signal transduction events.

This process leads to glycogen synthesis within the liver

Question 10

Outline the signal transduction mechanism for the glucagon receptor on liver cells:

Answer 10

Activation: Glucagon binds to its receptor (a G-protein-coupled receptor) on liver cells.

Pathway: Activates adenylate cyclase via the G-protein, increasing cAMP levels.

cAMP Role: cAMP activates protein kinase A (PKA).

Response: PKA phosphorylates target enzymes, leading to increased glycogen breakdown (glycogenolysis) and glucose production (gluconeogenesis), raising blood glucose levels.

Glucagon receptor signal transduction also contributes to lipolysis (breakdown of fat)

Question 11

What is the role of GLP-1?

Answer 11

GLP-1 is an agonist peptide ligand produced in the gut and acts on GPCRs on pancreatic B-cells

This leads to a signal transduction event leading to insulin secretion

Question 12

How do insulin, glucagon, and GLP-1 signal transduction networks work together to produce a coordinated biological response?

Answer 12

Insulin: Lowers blood glucose by promoting glucose uptake in muscle/adipose tissue and glycogen synthesis in the liver.

Glucagon: Raises blood glucose by stimulating glycogen breakdown and gluconeogenesis in the liver.

GLP-1: Enhances insulin secretion and inhibits glucagon release, while slowing gastric emptying and reducing appetite.

Coordination: Together, these hormones balance blood glucose levels, ensuring proper energy storage and availability based on the body’s needs.

Question 13

Define a receptor:

Answer 13

A cellular protein (or assembly of proteins) that control chemical signaling between and within cells is called a receptor

Question 14

Define a Ligand:

Answer 14

The general term given to a chemical substance that
specifically binds to a receptor is a ligand

Question 15

Define an agonist ligand:

Answer 15

A chemical substance (ligand) that binds to a receptor and activates it is called an agonist

Question 16

Define an antagonist ligand:

Answer 16

A chemical substance (ligand) that binds to a receptor and
prevents activation by an agonist is called an antagonist.

Question 17

Describe the signal transduction pathway for Receptor Tyrosine-Kinases (RTKs):

Answer 17

• agonist ligand binds
• receptor changes conformation and becomes activated
• receptor autophosphorylation occurs
• adaptor protein is phosphorylated

Question 18

What are the main differences between enzymes and receptors? (function and mechanism)

Answer 18

Function:
Enzymes catalyze chemical reactions, converting substrates into products. Receptors detect and bind ligands to initiate cellular responses.

Mechanism:
Enzymes lower activation energy and directly alter substrates, while receptors trigger intracellular signaling cascades without changing the ligand’s structure.