Extracellular receptor signalling Flashcards
what is the purpose of a signal transduction ?
- concerts one form of signal into another one
what are the 3 stages of a signal transduction ?
- extracellular signal activates membrane receptor
- alters intracellular molecules to be transduced via a certain pathway
- activates cellular response
what are first and second messengers in signal transduction?
- extracellular signal molecule is the 1st messenger
- while intracellular molecules are 2nd messenger
What types of chemicals can serve as extracellular signaling molecules (first messengers)?
- steroids
- peptides + proteins
- amines
- small molecules (ions)
What are the four main classes of receptors ?
- Ligand-gated ion channel
- G-protein coupled receptors
- Enzyme-linked receptors
- Nuclear receptors
what are ionotropic receptors + 2 examples ?
- form an ion channel pore
- type of ligand-gated ion channel
- Nicotinic acetylcholine receptor = Ach binds to receptor, opens channel for Na+ to enter
- GABA receptors = allow Cl- to enter, activated by benzodiazepines, inhibitory effect
What are metabotropic receptors?
- indirectly linked with ion channels, usually coupled with G protein
-eg. muscarin acetylcholine receptor
Compare the speed and duration of response for ionotropic and metabotrophic receptors ?
- metabotrophic is slower but longer lasting response
what is a G-protein coupled receptor (GPCR)?
- A receptor with 7 trans-membrane domains that activates G-proteins
what is the structure of G-protein ?
- made up of α, β, and γ subunits
- α subunit either has GDP or GTP attached
what happens to the G-protein when GTP binds to the α-subunit?
- when GTP binds to the α-subunit, the α-GTP dissociates from the βγ complex
Explain the G-protein cycle ?
- adrenaline (ligand) binds to β-andrenoceptor
- causes conformation change = GDP switched for GTP on α subunit
- α-GTP subunit dissociates
- α subunit activates adenyl cyclase
- converts ATP to cAMP which activates PKA
- GTP hydrolysed by GTPase
How does the G-protein cycle terminate?
- GTPase converts GTP to GDP
- inactivates protein
what enzyme hydrolyses cAMP (termination of signal transduction ?
- PDE (phosphodiesterase)
- cAMP coverted to AMP
what substance inhibits PDE ?
- caffeine
How does receptor desensitization reduce signal transduction ?
- PKA phosphorylates β-ARK
- β-ARK phosphorylates β-adrenoceptor
- reduces its affinity for adrenaline
what is the function of protein phosphatases ?
- remove phosphate groups
- opposite to kinase
what are the 3 main types of G proteins ?
- Gs
- Gi
- Gq
name a type of receptor that typically couples with Gs proteins.
- β-adrenergic receptors couple with Gs proteins.
Name a type of receptor that typically couples with Gi proteins.
- α2-adrenergic receptors couple with Gi proteins
What are the two types of Gα subunits that interact with adenylyl cyclase (AC)?
- Gαs: Stimulates AC so inc cAMP
- Gαi: Inhibits AC so dec cAMP
What is the role of Gq proteins ?
- activate phospholipase C (PLC)
- PLC cleaves PIP2 into IP3 and DAG
What are the products of PIP2 breakdown by PLC?
- A: Inositol trisphosphate (IP3) and diacylglycerol (DAG).
what is the role of IP3 ?
- iP3 binds to receptors on ER, stimulates ca2+ release
What is the function of DAG ?
- DAG remains in the membrane and activates protein kinase C (PKC), which phosphorylates target proteins.
do IP3 + DAG remain in membrane ?
-DAG hydrophobic so remains
- IP3 water soluble so moves to ER through cytosol
what intracellular proteins does calcium bind to and activate?
- Calmodulin (CaM)
- ## Ca2+-CaM complex activates CaMKs (CaM kinases)
what biological process are CaMKs involved in ?
- smooth muscle contraction
what is the role of α1 adreno-receptors in blood pressure regulation?
- cause vasoconstriction (smooth muscle contraction) via the Gq-PLC-IP3 pathway
- increasing blood pressure.
How do β2 adrenoceptors affect blood pressure?
- cause vasodilation via the Gs-cAMP-PKA pathway, - decreasing blood pressure.
What are the five subtypes of muscarinic receptors and their coupling?
- M1, M3, M5: Gq coupled (stimulatory)
- M2, M4: Gi coupled (inhibitory)
what are the 4 types of enzyme linked receptors ?
- receptor guanylyl cyclases
- receptor serine/theronine kinase
- receptor tyrosine kinase
- receptor tyrosine phosphatase
Describe the mechanism of action for receptor guanylyl cyclases + example of response
- ligand binding induces dimerization
- activates enzyme
- concerts GTP to cGMP
- cGMP activates kinases
- eg. vasodilation
Describe the mechanism of action for receptor serine/threonine example of response ?
- ligand binds to type 2
- type 1 binds to form ternary complex with type 2 and ligand
- type 2 activates type 1 via phosphorylation
- type 1 activates / phosphorylates proteins
- eg. cell proliferation
Describe the mechanism of action for receptor tyrosine kinase (RKT) example of response ?
- ligand binding causes receptor to dimersiation
- both receptors can phosphorylate each other
- recruit intracellular signal molecules
- eg. insulin
Describe the mechanism of action for receptor tyrosine phosphatase + example of response ?
- only has 1 transmembrane domain so no dimerisation
- ligand binding activates enzyme
- dephosphorylate target proteins
- eg. maturation of lymphocytes
