W3- Lecture 13.3- Receptors (pharma)

Question 1

Describe the structure of a kinase linked receptor (enzyme linked receptor)

Answer 1

Binding domain
Trans domain
Catalytic domain

Question 2

Describe an enzyme linked reaction

Answer 2

Ligand binding
Receptor dimerisation
Activation of catalytic domain, tyrosine residues become phosphorylated

Accessory proteins bind to complex (e.g. Proteins containing SH2 domains)
Intracellular pathways are activated (kinase cascade)
Transcription factors are activated

Question 3

Describe insulin activation of receptor tyrosine kinase

Answer 3

Insulin
binds to the α subunits of the insulin receptor
produces a conformational change in the receptor
activates tyrosine kinase in the β subunit, which causes autophosphorylation

Question 4

What can activated tyrosine kinase phosphorylate ?

Answer 4

proteins or enzymes that are involved in the physiological actions of insulin (decrease in blood glucose) including protein kinases, phosphatases, phospholipases, and G proteins

Question 5

Describe how receptor tyrosine kinase causes the suppression/synthesis of RNA

Answer 5

RTK activates a cascade of protein phosphorylation events that end up phosphorylation of transcription factors
Phosphorylated transcription factors enter the nucleus and bind to DNA
This activates or suppresses RNA for specific genes which contains transcription factors binding sites on their prompter region

Question 6

How long do the effects last of RTK on gene expression ?

Answer 6

long lasting effects on cell activity (Hours/days/ weeks )

Question 7

Name 4 classes of enzyme-linked reactions

Answer 7

Receptor tyrosine kinases (RTK)

Receptor serine/threonine kinases

Cytokine receptors

Guanylyl cyclase-linked receptors

Question 8

How are the following different to RTK

Receptor serine/threonine kinases
Cytokine receptors
Guanylyl cyclase-linked receptors

Answer 8

RTK- has tyrosine kinase enzyme activity + growth factor receptor + insulin receptor

Receptor serine/threonine kinases-kinase phosphorylates serine residues on target proteins

Cytokine receptors-Lack their own tyrosine kinase activity but ligand binding causes receptors to activate cytosolic tyrosine kinases

Guanylyl cyclase-linked receptors-intrinsic enzyme activity causes cGMP (cyclic GMP) formation

Question 9

Nuclear receptor
Type of protein
Found where
Structure

Answer 9

Globular protein
Found in cytosol
Binding domain -Transmembrane domain - DNA binding domain (zinc finger )

Question 10

Name a drug that treats COVID and acts on the Nuclear receptors
Exact receptor
+ effect

Answer 10

dexamethasone
Acts on the glucocorticoid receptor agonist (steroidal)
Inflammation, immunosuppressant

Question 11

Short description of how a Nuclear receptor acts

Answer 11

Ligand activated (transcriptional factors)
Receptor enters nucleus
Initiates gene transcription/ repression
Long term

Question 12

Name two ligands that can bind to a nuclear receptor

Why ?

Answer 12

Steroid + thyroid hormones

They have to be able to pass the membrane

Question 13

Name 1 nuclear receptor agonist

Action + use

Answer 13

Dexamethasone is a glucocorticoid receptor agonist, activation inhibits cycloxygenase-2 transcription and is a commonly used anti-inflammatory agent

Question 14

Name one nuclear receptor antagonist

Action + use

Answer 14

Tamoxifen is an oestrogen receptor antagonist used in breast cancer therapy