GPCR vs enzyme-linked receptors Flashcards
lecture 14
What was the first function discovered for G proteins?
Activating adenylyl cyclase through the α subunit
What are the two primary G protein subunits involved in regulating adenylyl cyclase?
αs: stimulates AC
αi: inhibits AC
Name four receptors that couple to Gs proteins.
β-adrenoceptors, vasopressin receptors, A2A adenosine receptors, and AB adenosine receptors.
Name four receptors that couple to Gi proteins.
α2-adrenoceptors, μ and δ opioid receptors, A1/3 adenosine receptors.
What class of G proteins activates phospholipase C (PLC)?
Gq proteins.
Name two key functions of Gq proteins.
Activating PLC and increasing intracellular Ca²⁺ levels.
How does cholera toxin (CTx) affect G protein signalling?
It ADP-ribosylates the as subunit, preventing GTP hydrolysis ad causing persistent activation.
What is the consequences of persistent activation of as in the colon?
Activation of PKA-dependent Cl- channels, leading to secretory diarrhoea.
How does pertussis toxin (PTx) affect G protein signalling?
It locks the ai subunit in an inactive state, preventing inhibitory control over AC/PKA.
What condition is associated with pertussis toxin’s action?
Whooping cough, due to increased cAMP and PKA activity in airways.
What does PLC cleave, and what are the products?
PLC cleaves PIP2 into IP3 in DAG.
What is the function of IP3 in Gq signalling?
It stimulates Ca2+ release from the endoplasmic reticulum.
What is the role of DAG in Gq signalling?
It recruits and activates protein kinase C (PKC) at the membrane.
How does PKC influence cellular response?
PKC phosphorylates proteins, potentiates IP3 effects, and regulates cell shape, proliferation, and transcription.
What protein binds Ca2+ to mediate intracellular responses?
Calmodulin (CaM), which binds 4 Ca2+ ions.
What does the Ca2+-CaM complex activate?
Phosphodiesterases (PDEs) and CaM kinases (CaMKs).
What is the role of CaMKs in smooth muscle contraction?
They phosphorylate target proteins, such as those involved in vasoconstriction
Which G protein pathway is involved in vasoconstriction?
Gq-PLC-IP3-CaMK via a1-adrenoreceptors.
Which G protein pathway is involved in vasodilation?
Gs-cAMP-PKA via B2-adrenoreceptors.
What are the 4 main types of enzyme-linked receptors?
Receptor guanylyl cyclases,
receptor serine/threonine kinases,
receptor tyrosine kinases (RTKs)
tyrosine-associated receptors
What do receptor guanylyl cyclases generate, and what is its function?
cGMP, which activates downstream kinases for responses like vasodilation.
How do receptor serine/threonine kinases (RTKs) signal?
Type II receptors phosphorylate type I receptors, activating SMAD proteins for cell proliferation.
What is a key example of RTK signalling?
The MAP kinase pathway.
What do tyrosine kinase-associated receptors rely on for activity?
Non-covalently associated tyrosine kinase proteins like JAK2.
How do receptor tyrosine phosphatases work?
They remove phosphate groups from tyrosine residues, modulating downstream signalling.
What is an example of guanylyl cyclase signallig?
Atrial natriuretic peptide (ANP) induces vasodilation via cGMP.
What is an example RTK signalling?
TGF-B mediated cell proliferation.
What is an example of tyrosine kinase-associated receptor signalling?
Cytokine signalling via the IL-acute phase response.
What is an example of receptor tyrosine phosphatase signalling?
CD45-induced lymphocyte maturation.
Name three mechanisms for terminating signal transduction.
Removal/inactivation of signals, inactivation of receptors, and degradation of second messengers.
How does caffeine affect signal termination?
It inhibits phosphodiesterases (PDEs), prolonging cAMP activity.
