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18 Cards in this Set

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1. If a ligand has a high affinity binding interaction with a receptor, would it require a higher or lower concentration [to achieve the target mechanism of the pathway] than a ligand that has a low affinity binding interaction with a receptor? Are the active concentrations of ligands usually high or low?
A high affinity ligand would require a lower concentration than a low affinity ligand to achieve the target mechanism of the pathway.
Active concentrations of ligands are very low
2. How long do ligands usually persist? (i.e., do they have long or short half-lives?) Why is this an important consideration for cell signaling?
Ligands have a very short half-life; most last for seconds, though some can last for days.
3. What is the cause and consequence of receptor desensitization? Name and describe three mechanisms of receptor desensitization.
Desensitization is the uncoupling of a receptor from its signaling cascade
This results from a receptor’s prolonged exposure to a ligand
1) Inactivation: receptor altered so that it disconnects from its cascade (e.g., inhibitory protein attaches to receptor)
2) Sequestration: receptor is temporarily internalized (by an endosome -> receptor-mediated endocytosis; vesicle fuses with endosome and receptor is recycled)
3) Down-regulation: after internalization, receptor is destroyed in lysosome (as it is not recycled)
4. Describe one way that GPCRs are desensitized. (Understand the type of desensitization, and the molecular mechanism of how it occurs.) What type of feedback is this? What would happen if arrestin was not functional, or GPCR phosphorylation did not occur?
GPCRs can be desensitized through inactivation
The GPCR is phosphorylated by GPCR Kinase (GRK), which causes binding by arrestin to the GPCR, desensitizing GPCR
This is a form of negative feedback
If arrestin was not functional or GPCR phosphorylation did not occur, the downstream signal would still be sent and the target mechanism activated
5. What is the difference between negative and positive feedback loops?
Negative: product of a pathway inhibits an earlier step in the same pathway
Positive: product of a pathway stimulates its own production or activation
6. What is cross-talk? Describe the difference between convergent and divergent cross-talk.
Cross-talk: integration of different pathways; one or more components of a signal transduction pathway affects another pathway
Convergent: different ligands signal to pathways that come together to elicit the same response
Divergent: Signals from the same ligand elicit different responses
7. What type of cross-talk is used to ensure an essential cellular target mechanism is accomplished? Why?
Convergent cross-talk
Convergent cross-talk is a fail-safe way to ensure mechanisms critical to life are achieved
8. How is divergent crosstalk used?
Higher order complex activities that are less essential for life
9. What kind of cross-talk does the MAPK pathway represent?
Divergent cross-talk
MAP KKK, MAP KK, and MAP K pathways are all activated by a single ligand to yield distinct cellular responses
10. What determines the extent of cross-talk in a given cell? Explain.
What genes are expressed within a cell determine the extent of cross-talk
Any cellular response/mechanism is determined by genetic regulation
11. What is one mechanism used to prevent cross-talk? Explain.
Scaffolds that hold scaffolding proteins prevent cross-talk
When scaffolds hold proteins in place, the proteins are prevented from participating in other pathways
12. What are examples of processes that require more than one signal? Describe each.
Neuron signaling: neurons secrete neurotransmitters across synapses to downstream neurons; single neurons have many synaptic inputs
Immune functions: require multiple inputs; safe-guard to ensure that our immune system does not attack our own cells
Cell division: multiple required signals
13. How do multiple signaling events/inputs contribute to neuronal signaling?
A single neuron has many synaptic inputs (thousands of nerve terminals)
Each receptor activation changes the ion flow of the downstream neuron
14. Why are multiple signaling events/inputs so important for immune system signaling?
They serve to fine-tune signaling
Safe-guard so that the immune system does not attack our own cells
15. What are the multiple signals that contribute to cell division?
Growth factors, cytokines, and hormones
Anchorage dependence (cells need to be anchored to other cells or ECM to divide)
Density-dependent inhibition (crowded cells will not divide)
What is ligand-receptor affinity defined by?
Kinetics of association and dissociation
Define the term dissociation constant. As the dissociation constant increases, affinity ________________.
Dissociation constant: the concentration of ligand required to bind half the receptors.
Glycogen breakdown in the liver is an example of which kind of cross-talk? Describe.
Convergent cross-talk.
Critical function to provide blood glucose between feedings (homeostasis)
Vasopressin from neural pituitary and Glucagon from pancreas guarantee appropriate glucose levels.