Intracellular Signalling Pathways Flashcards
What is signal transduction?
extracellular/Intracellular receptors, ligand binding, generates response
What are the 3 receptor superfamilies?
GPCRs.
Ligand-gated ion channels.
Receptors with intrinsic enzymatic activity
Describe what a ligand is
term used for something that interacts with a receptor without knowing what it does, binding activates, directly/indirectly brings about change
What is the difference between and agonist and an antagonist?
Antagonist: bind to receptor = do not activate it (high degree of affinity but no efficacy) = blocks effects of agonist
Agonist: bind to receptor = activate it = intracellular transduction
What does GPCR stand for?
G protein-coupled receptors
What is the structure of a GPCR?
7 transmembrane regions. Linked by short sequences. N + C terminal –> variation in size of GPCR comes from size of N + C.
Binding: buries between AA side chins in middle of TM proteins, or at N terminus
List the stages of how a GPCR works
Ligand binds, changes conformation of receptor = interaction with G protein (specific), G protein activates, exchange of GDP –> GTP on Gα subunit, α and βγ subunits dissociate (type of subtype = diff signalling) –> each can interact with effector proteins (effector).
Termination: α subunit GTPase activity hydrolyses GTP –> GDP. α-GDP and βγ subunits reform to inactive complex
Where does GPCR ligand binding take place?
The cell membrane
How does cholera work?
toxin = GTPase unable to hydrolyse GTP, permanent on state = high levels cAMP
How does pertussis work?
stops GDP swapping for GTP
What is cAMP?
α-GTP (from GPCR pathway) stimulates adenylyl cyclase, ATP changes to cyclic AMP, cAMP exerts actions through cyclic AMP-dependent protein kinase (PKA): secondary messenger
What is PKAs structure?
4 subunits. 2 – R: regulate activity of C units. 2 – C: catalytic (kinase activity). Catalytic C subunits phosphorlyates target proteins in cell
Activated by the binding of 4 cAMP.
Via what method is Ca2+ increased in the cell from across the cell membrane?
LGIC: ligand gated ion channel, most activated by neurotransmitters, they bind = open, influx of Ca2+.
VOCC: voltage operated Ca2+ channel, depolarisation allows Ca2+ to flow down conc gradient.
SOC: Ca2+ sensor on ER/SR detects storage is low, gives off SER signal, SOC channel lets Ca2+ in
How is Ca2+ increased from the ER/SR?
Ryanodine receptors: Ca2+ induced Ca2+ release (CICR)
IP3R: α-GTP (from GPCR pathway) stimulates phospholipase C = cleavage of PIP2 –> IP3 (secondary messenger) + DAG, IP3 binds ER/SR receptors = Ca2+ release from storage = increase conc 5-10 fold
How is [Ca2+] lowered in the cell?
PMCA: use 1 ATP to transfer 1 Ca2+ out of cell
NXC: (Na/Ca exchanger) 3 Na+ in for 1 Ca2+ out
SERCA: use 1 ATP to transfer Ca2+ into ER/SR storage
