GPCR Signalling Flashcards
What are G protein-coupled receptors (GPCRs)?
The largest family of cell surface receptors, comprising over 800 in humans.
What is the structure of GPCRs?
They have 7 transmembrane spans across the lipid bilayer.
What are the three subunits of trimeric G proteins?
- α
- β
- γ
How are G proteins activated?
When bound to GTP.
What happens when G proteins hydrolyze GTP?
They become inactive by converting GTP to GDP.
What is a second messenger?
A rapidly produced diffusible signalling molecule that activates effector proteins.
What is the effect of GPCR-mediated activation of G proteins?
Targets include ion channels and membrane-bound enzymes.
What role do second messengers play in signal transduction?
They amplify the signal rapidly and are inactivated quickly.
What is the function of adenylyl cyclase?
Converts ATP into the second messenger cAMP.
What are the second messengers produced by phospholipase C?
- DAG
- IP3 (cleaved from PIP2)
What is the role of Protein Kinase C (PKC)?
Activated at the membrane and involved in various signaling pathways.
What is the significance of Ca2+ in GPCR signaling?
Regulates effector proteins through calmodulin.
What is the principle of signal transduction related to termination?
Signaling must be terminated; this involves receptor internalization and degradation.
Fill in the blank: cAMP is rapidly inactivated by _______.
Phosphodiesterase
True or False: Second messengers are not involved in amplifying the signal.
False
What is the role of guanine exchange factors (GEF) in GPCR signaling?
They facilitate the activation of G proteins.
What is the role of regulators of G protein signaling (RGS)?
They help in the inactivation of G proteins.
What is the function of diacylglycerol (DAG)?
It acts as a second messenger involved in activating PKC.
What is the relationship between ligand binding and cellular response?
The more ligand binding, the greater the cellular response.
What type of kinase is Protein Kinase A (PKA)?
A serine-threonine protein kinase.
What triggers the release of Ca2+ as a second messenger?
The activation of IP3.
What are the main groups of phospholipases C?
- PLCγ
- PLCδ
- PLCβ
What is the main lipid content of cellular membranes that phospholipases act upon?
Phosphatidylcholine and phosphatidylinositol.
What is the result of increased Ca2+ levels in cells?
Altered target protein activity, including activation of CaMK.
What is the function of inositol phospholipids in signaling?
They dynamically regulate signaling pathways in response to extracellular signals.
What activates GPCRs?
Extracellular ligands
E.g. Glucagon, adrenaline, dopamine, histamine
What inactivates GPCRs?
Phosphorylation and internalisation
Residues that can be phosphorylated are serine, tyrosine and threonine only
What are trimeric G proteins?
In the inactive state, the G protein consists of a trimeric complex located in the plasma membrane
In the active state, the trimeric G protein complex can dissociate —> alpha dissociates from beta/gamma complex
What happens when G proteins interact with ion channels?
Causes an immediate change in cell behaviour
What happens when G proteins interact with membrane bound enzymes?
Enzyme activation leads to the production of intracellular signalling molecules that act as second messengers
PKA and gene transcription
- Activation of PKA in the cytosol
- Translocation to the nucleus
- Phosphorylation of transcription factors
- Increased or suppressed transcription of target genes
Inositol phospholipids
How is DAG and IP3 involved in Protein kinase C translocation?
- PKC is recruited to the membrane from the cytosol
- DAG brings the PKC to the membrane
- PKC is activated at the membrane but not fully
- IP3 triggers release of Ca2+ from the endoplasmic reticulum
- The released Ca2+ binds to PKC and fully activates it
Structure of conventional PKC
Other PKCs
Novel PKC, group B —> do not have a C2 = Ca-independent and PL sensitive
Atypical PKC, group C —> do not have a C1 and are missing a part of C2 = Ca-independent and PL insensitive
