Cytokine receptor Flashcards
What are the effector properties of cytokines
Pleiotropic(diff effects on diff types of target cells)
- Redundancy (multiple cytokines hv same effect)
- synergistics (cooperative effect)
- antagonistic (inhibition by one another)
How many classes in cytokine recep
I (classical), II (TNF), III (IL-1)
TNF full form
tumour necrosis factor
How many types of class I cytokine recep
Type I and II
How many types of type I classical
- Single chain recep fml
- Common y chain recess fml
- Gp130 recep fml
- common Bchain recep fml
Exp of type I single chain recep
Erythropoietin
Exp of type I common ychain recep
IL-2 fml + IL-4
Exp of type I Gp130 recep
IL-6
Exp of type 1 Bchain recep
IL-5
Exp of Type II classical recep
IFNy
Diff btw type I and II classical
Type I has conserved WSXWS motif on extracellular domain
How classical cytokine recep activated by erythropoietin
dimerisation, JAK-STAT pathway activated
What happen when erythropoietin recep ACTIVATED
JAK-2 phosphorylates Tyr on intracellular domain of EpoR
- Activated Tyr as docking sites of STAT5 via its SH2 domain
- STAT5 phosphorylated by JAK2, form dimers
- STAT5 activates gen transcription
Tm for Rheumatoid arthritis
Oral Tofacitinib high potency in inhibiting JAK1 & 3, prevent STAT translocation into nucleus
Tofacitinib side effect
- Increased risk of shingles infection
- Anaemia, when JAK2 activity affected
JAK-1 specific inhibitor
Abrocitinib
JAK-STAT regulation
- SHP-1 removes P from JAK
- PIAS binds to activated STAT prevent DNA binding
- SOCS produced by STAT activated gene transcription, binds to Tyr-P on JAK/receptor
- SUMO binds to STAT affect its stability
Exp of Class II (TNFR)
TNFR1, RANK
RANK full form
Receptor activator of NF-kappaB
Ligand of TNF1 and RANK
TNFa, RANKL
What are the two pathways TNFR1 can activate
Inflammatory and death-inducing
Pathways of inflammatory TNFR1
MAPK activation, NF-kappaB activation
Pathway of death-inducing pathway of TNFR1
Pro-caspase 8/10 activation