W3- Lecture 13.3- Receptors (pharma) Flashcards
Describe the structure of a kinase linked receptor (enzyme linked receptor)
Binding domain
Trans domain
Catalytic domain
Describe an enzyme linked reaction
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
Describe insulin activation of receptor tyrosine kinase
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
What can activated tyrosine kinase phosphorylate ?
proteins or enzymes that are involved in the physiological actions of insulin (decrease in blood glucose) including protein kinases, phosphatases, phospholipases, and G proteins
Describe how receptor tyrosine kinase causes the suppression/synthesis of RNA
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
How long do the effects last of RTK on gene expression ?
long lasting effects on cell activity (Hours/days/ weeks )
Name 4 classes of enzyme-linked reactions
Receptor tyrosine kinases (RTK)
Receptor serine/threonine kinases
Cytokine receptors
Guanylyl cyclase-linked receptors
How are the following different to RTK
Receptor serine/threonine kinases
Cytokine receptors
Guanylyl cyclase-linked receptors
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
Nuclear receptor
Type of protein
Found where
Structure
Globular protein
Found in cytosol
Binding domain -Transmembrane domain - DNA binding domain (zinc finger )
Name a drug that treats COVID and acts on the Nuclear receptors
Exact receptor
+ effect
dexamethasone
Acts on the glucocorticoid receptor agonist (steroidal)
Inflammation, immunosuppressant
Short description of how a Nuclear receptor acts
Ligand activated (transcriptional factors)
Receptor enters nucleus
Initiates gene transcription/ repression
Long term
Name two ligands that can bind to a nuclear receptor
Why ?
Steroid + thyroid hormones
They have to be able to pass the membrane
Name 1 nuclear receptor agonist
Action + use
Dexamethasone is a glucocorticoid receptor agonist, activation inhibits cycloxygenase-2 transcription and is a commonly used anti-inflammatory agent
Name one nuclear receptor antagonist
Action + use
Tamoxifen is an oestrogen receptor antagonist used in breast cancer therapy