Receptors and Signal Transduction Mechanisms Flashcards
(32 cards)
List the four major types of receptors
- Ion channels
- G protein coupled receptors
- Enzyme linked receptors
- Intracellular receptors
List the 6 major steps involved in cell signalling
- Synthesis and release of signalling molecules
- Transport to the target cells
- Detection of the signal by a specific receptor protein
- A change in cellular metabolism
- Change in cell activity
- Removal of the signal
When a drug interacts with a receptor, what three things happen?
- Conformational changes in receptor
- Transduction of the signal via alterations in cytosolic metabolism
- Changes in cell function and gene transcription
Describe the conformational selection model of receptor-drug interactions.
Receptors exist in multiple conformational states and binding of a drug stabilizes one or more of these conformations
This way, drugs can switch a population of receptors into the active state, and the number of receptors never changes (duh..)
Describe the induced fit model of drug-receptor interactions.
The initial interaction between receptor and ligand is weak, but interactions induce conformational changes in the receptor that enhance the affinity of drug for receptor and transition to the active ligand-receptor signaling complex.
What is the orthosteric site on a receptor? A site where a ligand can bind that is not orthosteric is ___?
The active site
Other sites are allosteric
What is the advantage of allosteric modulation of receptors?
That you don’t often get toleration or side effects of orthosteric ligands
True or false? You often need binding on two subunits (both binding sites) for biological effect with ionotropic receptors.
TRUE
What type of receptors exist at neuromuscular junctions?
Nicotinic receptors
Which G protein family are most drugs acting on?
Rhodopsin like family of GPCRs
List some common GPCR effector molecules
- Adenylyl cyclase
- Phospholipase C/A
- cGMP phosphodiesterase
- Potassium channels
- Calcium channels
Describe the three subunits of a G protein in the inactive state and active state
Inactive: GDP alpha bound with β and γ subunits
Active: GTP α, β and γ dissociate from alpha but remain together
What are GAPs?
Accessory proteins in G protein activation (GTPase accelerating protein)
- Enhance the OFF rate (hydrolysis of GTP to GDP)
- Enables the system to reset
- Act through regulators of G protein signalling
Describe the components involved in GPCRs in order of their involvement. (4)
- Receptor
- G protein (GTPase)
- Effector molecule
- Second messenger
What do the four main G proteins do?
Giα: inhibits cAMP phospholipases
Gsα: Increases cAMP
Gqα: Increases DAG and IP3
G12,13α: Activates Rho
What is Rho in GPCR signalling?
Rho is another G protein important in causing changes in cellular structure.
What is the most redundant part of GPCR signalling?
Ligand receptor interaction (after that things can get very complex!)
What two phenomena can result in different effects from G proteins?
- GPCR complexes
- Crosstalk
What do the second messengers IP3 and DAG do?
IP3: Stimulates release of calcium from the smooth endoplasmic reticulum
DAG: Activation of PKC, opening calcium channels on cell membrane
What is signalling convergence?
When two signalling pathways converge to produce an integrated effect, which is dependent on which pathway is strongest.
Describe the CREB response.
CREB (cAMP response element-binding protein)[1] is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the downstream genes
True or false? Frequent rises in cAMP in a cell results in desensitization.
True
What is βArr?
Beta arrestin, the receptor that binds with GRK (G protein receptor kinase) to cause HOMOLOGOUS desensitization through internalization
Leads to clathrin mediated internalization and degradation/recycling.
What is heterologous desensitization of GPCRs?
Desensitization through PKA or PKC (or other such proteins)
