Intro to Receptors and Signaling Flashcards
What is signal transduction?
When an extracellular signaling molecule activates a cell surface receptor, causing the receptor to alter second messengers to transmit the signal and elicit a physiologic response.
What is an orphan receptor?
An apparent receptor that has a similar structure to other identified receptors but whose endogenous ligand had not yet been identified
What are the 4 types of receptor superfamilies?
Type 1: Ligand-gated ion channels
Type 2: G-protein coupled receptors (GPCR)
Type 3: Kinase-linked and related receptors
Type 4: Nuclear receptors
Ligand Gated Ion Channels
- What is their rate of transmission of the signal?
- Describe their structure.
- What is a common example?
- Fast synaptic transmission
- Four - 5 subunits with transmembrane alpha helices arranged around central aqueous channel
- Neurotransmitter receptors, i.e. nicotinic and acetylcholine receptors
G-Protein Coupled Receptors
- Describe their structure.
- What are the 3 subunits of the G-protein portion of the receptor (intracellular)?
- Which of these subunits has GTP-ase activity?
- What is an example of this receptor family?
- 7 membrane spanning alpha helices
- Alpha, Beta, Gamma
- Alpha
- Histamine receptors
GPCR Types
Gas
Gai
Gaq
Ga12/13
Gbeta/gamma
Describe how GPCR receptors work.
Resting state - Receptor imbedded in membrane, G-protein consists of all 3 subunits which are bound together and anchored in membrane near receptor
Ligand Binding - ligand binds to receptor –> conformational change –> allows association with G-protein –> association of alpha subunit with receptor bound to ligand produces change in shape of G-protein –> GDP bound to alpha subunit is exchanged for GTP
Activation of Target Proteins - Alpha subunit dissociates from receptor and Beta/Gamma subunits, migrates to target protein and interacts with it (effect depends on type of receptor). The Beta/Gamma subunit will either remain bound to the receptor or it may also migrate to a different target and activate it.
Restoration of Resting State
GTP-ase activity of alpha subunit increases when bound to target protein –> GTP converted to GDP + Pi –> alpha subunit reunites with Beta/Gamma and remains imbedded in membrane near receptor again.
What are 5 common targets for G-proteins.
Adenylyl Cyclase
Phospholipase C
Ion Channels
rho A / rho kinase
MAPK
What is the speed of a GPCR signaling pathway? How long do the effects last?
Slow
Long-lasting effects due to cascade nature of activation of multiple messenger molecules to produce response
Describe how GPCR signaling produces amplification of the initial signal.
Enzyme Linked Receptors
- Ligand is often a ___ ___
- The Enzyme that is involved is often ___ ___
- Describe the structure
- What is an example of this kind of receptor?
- Growth Factor
- Tyrosine Kinase
- Large extracellular ligand binding domain connected via single transmembrane helix to intracellular domain
- Insulin receptor
Describe the general process of signal transduction for enzyme linked receptors.
Ligand binds to receptor –> receptor dimerizes with another receptor –> intracellular tyrosine kinases phosphorylate eachother –> activated TyrKinase –> Phosphorylate other messenger proteins to illicit response
What are the 2 important pathways of enzyme linked receptors?
MAPK - important in cell division, growth, differentiation
Jak/Stat - activated by cytokines, control synthesis and release of inflammatory mediators
Describe the MAPK activation of enzyme linked receptors.
Describe Jak/Stat activation of enzyme linked receptors.
