Cell Signalling II

Question 1

What does the strength of a response depend on?

Answer 1

Concentration of messenger/ligand

Number of receptors per target cell

Receptor affinity for messenger

Question 2

What is Agonist?

Answer 2

Chemical which binds to receptor

Action mimics normal response

Question 3

What is Antagonist?

Answer 3

Chemical which binds to receptor
Binding does not result in response
Competes with normal ligand

Question 4

What is examples of receptor antagonist and agonist?

Answer 4

Beta-endorphin = endogenous opiate
- Beta-endorphin binds to mu opiate receptors producing
analgesia

Question 5

What is Down Regulation?

Answer 5

Receptor number decreases on target
May result from excess messenger
Sensitivity to messenger decreases
Tolerance to messenger develops

Question 6

What is Up Regulation?

Answer 6

Receptor number increases on target
May result from too little messenger
Sensitivity to messenger increases

Question 7

What are intracellular receptors?

Answer 7

Receptors for lipophilic messengers usually located in the cytosol or the nucleus of target cells

Question 8

What are Cell surface receptors?

Answer 8

Receptors for liphophobic messengers that cannot permeate the plasma membrane

• Ion-channel coupled receptors
• G-protein-coupled receptors
• Enzyme-coupled receptors

Question 9

What do intracellular receptors include receptors for?

Answer 9

• Steroid hormones : derived from cholesterol and include cortisol, vitamin D and steroid sex hormones.
• Thyroid hormones : derived from the amino acid tyrosine
• Retinoids : derived from Vitamin A (retinol); ex: retinoic acid

Question 10

What do cytoplasmic receptors do when activated?

Answer 10

when activated by the ligands they enter the nucleus through nuclear pores complexes

Question 11

What is the function intracellular receptors?

Answer 11

They all have a related structure

They Act as transcription factors  bind to response elements  influence gene transcription

Cell response is via increasing or decreasing the rate of gene expression

Question 12

What is DNA binding domain?

Answer 12

DNA-binding domain in each receptor around 60 a.a. , flanked by a C terminal regulatory domain

At the N terminal variable region known as the A/B domain (variable between receptors), ranging between 50 to over 500 a.a in human

Question 13

What is Ligand binding domain?

Answer 13

200-250 a.a, also responsible for the association of heat shock proteins

Question 14

What is the Nuclear Localisation Sequence?

Answer 14

Responsible for the localisation of the receptor to the nucleus

Question 15

What are the characteristic structural elements of a nuclear receptor structure?

Answer 15

DNA-binding domain

AF1 and AF2: transcription Activation Function 1 and 2

NLS : Nuclear localisation sequence

Question 16

Explain the Mode of Action of Intracellular Receptor I?

Answer 16

The ligands penetrate the cell membrane

Bind to their receptors in the cytoplasm

The ligand receptor complexes oligomerize and accumulate in the nucleus

In the nucleus, the ligand receptor complexes bind to the hormone responsive element (HRE) on DNA and act as transcription factor

Question 17

Explain the Mode of Action of Intracellular Receptor II?

Answer 17

Some Intracellular receptors are often found in the cytoplasm in an inactive complex bound to heat-shock proteins (Hsps)

Question 18

Explain Signal transduction mechanisms for response mediated by intracellular receptors? (1)

Answer 18

1a- If a receptor is located in the nucleus , the hormone diffuses into the nucleus and binds to it, forming a hormone-receptor complex

1b- If a receptor is located in the cytosol, the hormone binds to it there, forming a hormone-receptor complex that enters the nucleus

Question 19

Explain Signal transduction mechanisms for response mediated by intracellular receptors? (2)

Answer 19

2-Inside the nucleus, the complex binds HRE, located on a specific gene

3- Binding of the complex to the HRE, activates or deactivates gene transcription

Question 20

Explain Signal transduction mechanisms for response mediated by intracellular receptors? (3)

Answer 20

4- In this example, binding of the complex activates gene transcription, resulting in synthesis of mRNA whcih moves out into the cytosol

5- The mRNA is translated by the ribosomes