Drug Targets: Kinase-Linked / Nuclear Receptors Flashcards
(15 cards)
What is phosphorylation’s role in kinase-linked receptor signaling?
It regulates protein activity by adding phosphate groups to tyrosine, serine, or theronine residues
What happens after phosphorylation of tyrosine residues?
Proteins with SH2 domains bind, triggering further phosphorylation and activation of downstream signalling pathways
What biological processes are kinase-linked receptors involved in?
Cell growth
Differentiation
Regulation of gene transcription
How does EGFR contribute to cancer therapy resistance?
Tumour cells can reactivate the kinase cascade even without EGFR activation, leading to resistance
How can EGFR be inhibited?
Using antibodies and small-molecule inhibitors to block its activity
How do nuclear receptors regulate gene transcription?
The drug-receptor complex binds to hormone response elements in gene promoters, activating or repressing gene transcription
How does nuclear receptor activation affect protein levels?
Changes in mRNA transcription lead to differences in protein expression
What ae the key structural fatures of nuclear receptors?
Soluble receptors (cytosolic or nuclear)
C-terminal ligan binding domain, N-terminal DNA-binding domain
Monomeric, consisting of 400-1000 amino acids
Zinc-finger motifs for DNA binding
What is the role of coactivators in transcription?
They have histone acetyltransferase activity, loosening histones from DNA, promoting gene transcription
What do corepressors do?
They help recruit histone deacetylases, tightening histone associations with DNA and repressing transcription
What is the purpose of the solvent control in Western blot experiments?
Ensures observed effects are due to the drug and not the solvnt itself
What is the significance of probing for Sodim Potassium ATP Synthase, Beta-Tubulin, and Histone H3?
These serve as loading controls and confirm purity of different subcellular fractions
What does Western blotting reveal about glucocorticoid receptor (GR) localisation?
GR is absent from the membrane but present in cytosolic and nuclear fractions.
Drug 7 enhances nuclear translocation, suggesting increased transcriptional activity
How is dosing determined from pharmacokinetic analysis?
Based on maximum serum concentration, time to peak, half-life, and minimum effective concentration
Why might drug Y be preferable over drug X?
It promotes greater nuclear translocation, potentially enhancing transcription regulation.
Its lower plasma conentration may reduce off-target effects
