L10 GPCR Signalling Flashcards
Effectors of trimeric G proteins
enzymes
What do the effector enzymes of G proteins create
2nd messengers and ion channels
IP3
diffusible second messenger
IP3 function
controls calcium levels
Gqa receptors
a-adrenergic amines, Ach, various neurotransmitters
Gqa effectors
activate phospholipase Cb to produce IP3
What type of signalling is shared across many receptor families
signalling via lipid derived second messengers
Advantage of shared lipid signalling
cross talk and amplification
Lipid derived second messenger examples
PIP2, phosphatidylcholine, sphingomyelin
What targets membrane lipids
receptor regulated lipases
What are the two types of 2nd messengers derived from membrane lipids
i - water soluble, ii - hydrophobic molecules
Movement of water soluble lipid derived 2nd messengers
diffuse through the cytoplasm
Movement of hydrophobic lipid derived second messengers
remain in membrane
Function of lipid kinases
add phosphate groups to lipids
DAG
diacylglycerol
DAG structure
two fatty acid chains covalently bonded to a glycerol molecule through ester linkages
What is the more abundant lipid derived second messenger
Phosphatidylcholine
Example of hydrophobic 2nd messenger
DAG
Function of DAG
control signalling that occurs in PM
GPCR activation of PLC generates…
IP3 and DAG
What does specificity in signalling come from
selective expression and cellular localisation of signalling molecules
PH domain function
anchors parts of enzyme into PM
What is the PH domain important for
recognition
What is PKC regulated by
diaceylglycerol and calcium
Why is the location of a kinase important
it can only phosphorylate proteins near it
What are PKCs
ser/thr kinases
What is the PKC C1 domain activated by
DAG
What is the PKC C2 domain activated by
Ca2+
What is PMA
phorbol ester analogue of DAG
PMA function
activate PKCs
What does GFP tagged PKC imaging show
agonist dependent translocation to PM
What does PKC have built in
inhibitory peptide
Location of inhibitory peptide in PKC
when resting - folded into catalytic domain of kinase
What residues cannot be phosphorylated
alanine residues
Effect of phosphorylation
switches ON/OFF a function
What does DAG binding to PKC cause
dissociation of intramolecular pseudosubstrate domain from active site
What can phosphorylation of receptors contribute to
desensitisation
Function of munc13
controls docking of secretory vesicles at PM
What recruits munc13
activation of GqPCRs and synthesis of DAG in PM
What causes Lowe syndrome
mutations in OCRL
How is a large chemical gradient for calcium created
proteins in lumen of ER bind up Ca2+
How is calcium influx into the cytosol regulated in the PM
voltage and ligand gated channels
What is STIM
protein in ER that senses calcium