Pharmacology - Catalytic & Nuclear Receptors Flashcards
What are catalytic receptors made out of?
cell-surface proteins, usually dimeric in nature, which encompass ligand binding and functional domains typically in one polypeptide chain
What does dimerisation lead to?
activation
Define dimerisation in receptor:
a general mechanism to increase binding site affinity, specificity, and diversity
RTK
Receptor Tyrosine Kinase
Name Receptors for growth factors:
Epidermal growth factor- EGF
Vascular endothelial growth factor-VEGF
Insulin
Neurotrophins
Insulin-like growth factor- IGF
Platelet-derived growth factor- PDGF
& many others
What does activation of receptor lead to?
cell proliferation, differentiation, survival and metabolism
What doe HYPERactivation lead to?
to polyps, tumour and cancer
Growth factor binding RTK, leads
dimerization and autophosphorylation
One tyrosine kinase ______ autophosphorylation of its partner and vice versa
activate
- Signalling proteins recruited to RTK
- Signalling proteins contains SH2 domain to sense and bind specific RTK (specificity)
once ligand binds to receptor [extracellular] =
dimerisation > autophosphorylation > activation of downstream signalling [mostly intracellular]
Some SH2 domain proteins are enzymes
directly produce signals: e.g. phospholipase C- activation leads intracellular
Some SH2 domain proteins are adaptors
They link the RTK with the signalling protein
-e.g. Grb2 links between EGF receptor and SOS, a regulator of the Ras-MAP kinase pathway (will learn Ras-MAP kinase in details in the progressive years)
Signal 1
proliferation
Signal 2
Survival
Receptor Tyrosine Kinase (RTK)- drugs
Very limited
Insulin: life saving drug (in PCL III, revisit insulin’s RTK signalling
Many neurotrophin analogues couldn’t pass through clinical trials (failures)
Monoclonal antibodies