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Questions and Answers
What is the main role of enzyme cascades during signal amplification?
What is the main role of enzyme cascades during signal amplification?
What happens to the number of active G proteins when a single hormone binds to a receptor?
What happens to the number of active G proteins when a single hormone binds to a receptor?
How does cyclic AMP (cAMP) contribute to signal transduction?
How does cyclic AMP (cAMP) contribute to signal transduction?
What is the approximate amplification factor that can occur with a single hormone molecule?
What is the approximate amplification factor that can occur with a single hormone molecule?
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What is the role of phosphorylase kinase in the amplification process?
What is the role of phosphorylase kinase in the amplification process?
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What activates adenylyl cyclase in the signaling pathway?
What activates adenylyl cyclase in the signaling pathway?
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What is the role of cAMP in cellular signaling?
What is the role of cAMP in cellular signaling?
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Which enzyme rapidly converts cAMP to AMP to help eliminate the signal?
Which enzyme rapidly converts cAMP to AMP to help eliminate the signal?
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What is the primary function of protein kinase A (PKA) in the signaling pathway?
What is the primary function of protein kinase A (PKA) in the signaling pathway?
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What initiates the activation of the G-protein linked receptors?
What initiates the activation of the G-protein linked receptors?
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Which part of the G-protein complex completes the heterotrimer?
Which part of the G-protein complex completes the heterotrimer?
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What occurs to Gα after it binds to GTP?
What occurs to Gα after it binds to GTP?
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Which residues does PKA phosphorylate in target proteins?
Which residues does PKA phosphorylate in target proteins?
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What is the role of gene regulatory proteins in cellular signaling pathways?
What is the role of gene regulatory proteins in cellular signaling pathways?
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Which of the following is a signaling pathway that is triggered by adrenaline?
Which of the following is a signaling pathway that is triggered by adrenaline?
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What does phospholipase C (PLC) cleave to trigger intracellular signaling?
What does phospholipase C (PLC) cleave to trigger intracellular signaling?
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What are the second messengers produced from phospholipase C activity?
What are the second messengers produced from phospholipase C activity?
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Which of the following biological processes can be triggered by Ca2+ as an intracellular messenger?
Which of the following biological processes can be triggered by Ca2+ as an intracellular messenger?
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How does Protein Kinase C (PKC) primarily respond after activation?
How does Protein Kinase C (PKC) primarily respond after activation?
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What effect does the release of Ca2+ ions have on cellular functions?
What effect does the release of Ca2+ ions have on cellular functions?
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Which substance is NOT produced as a result of PLC activity?
Which substance is NOT produced as a result of PLC activity?
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What role do scaffolding proteins play in signaling efficiency?
What role do scaffolding proteins play in signaling efficiency?
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Which of the following describes how a G protein shuts off the signal?
Which of the following describes how a G protein shuts off the signal?
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What happens to a receptor when signal molecules leave it?
What happens to a receptor when signal molecules leave it?
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How does pathway branching affect cellular responses?
How does pathway branching affect cellular responses?
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What is the function of phosphodiesterases in cell signaling?
What is the function of phosphodiesterases in cell signaling?
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Which feature defines the specificity of cell signaling?
Which feature defines the specificity of cell signaling?
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During self-inactivation in G-protein signaling, what directly leads to the signal being turned off?
During self-inactivation in G-protein signaling, what directly leads to the signal being turned off?
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What is indicated by the term 'cross-talk' in cell signaling?
What is indicated by the term 'cross-talk' in cell signaling?
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What effect do caffeine, theophylline, and theobromine have on cAMP levels?
What effect do caffeine, theophylline, and theobromine have on cAMP levels?
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How is the signal turned off after receptor activation via a G-protein?
How is the signal turned off after receptor activation via a G-protein?
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What role does protein phosphatase play in cellular signaling?
What role does protein phosphatase play in cellular signaling?
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What is a consequence of Vibrio cholerae's enterotoxin on the G-protein signaling pathway?
What is a consequence of Vibrio cholerae's enterotoxin on the G-protein signaling pathway?
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Which biological process does a rise in intracellular Ca2+ primarily trigger?
Which biological process does a rise in intracellular Ca2+ primarily trigger?
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What is the function of β-arrestin in the signaling pathway?
What is the function of β-arrestin in the signaling pathway?
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What is the role of cAMP in improving memory?
What is the role of cAMP in improving memory?
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What happens when intracellular signaling cascades are not turned off effectively?
What happens when intracellular signaling cascades are not turned off effectively?
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Study Notes
G-Protein Coupled Receptors (GPCR)
- GPCRs are cell surface receptors that bind to extracellular signaling molecules and activate intracellular signaling pathways.
- GPCRs have seven transmembrane helices and interact with heterotrimeric G-proteins for activation.
Heterotrimeric G-proteins
- G-proteins are made of three subunits: α, β, and γ.
- The α subunit binds to GDP in its inactive state.
- Upon activation, the α subunit releases GDP and binds to GTP, leading to the dissociation of the β and γ subunits.
Adenylyl Cyclase Pathway
- The activated α subunit can activate adenylyl cyclase, which catalyzes the conversion of ATP to cyclic AMP (cAMP).
- cAMP is a second messenger that activates protein kinase A (PKA).
- PKA phosphorylates target proteins, altering their activity.
Inositol Phospholipids Pathway
- Some G-proteins activate phospholipase C instead of adenylyl cyclase.
- Phospholipase C cleaves phosphatidylinositol, generating two second messengers: inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG).
- InsP3 triggers the release of calcium ions (Ca2+) from intracellular stores.
- DAG activates protein kinase C (PKC).
- Increased Ca2+ and PKC activation lead to various cellular responses, including cell growth, cytoskeleton regulation, and protein secretion.
Signal Amplification
- Enzyme cascades amplify the cell's response by multiplying the number of activated molecules at each step.
Signal Specificity
- Different cells respond differently to the same signal due to variations in their proteins and pathways.
- Pathway branching and "cross-talk" allow for the coordinated integration of multiple signals.
Signal Efficiency
- Scaffolding proteins increase the signal transduction efficiency by bringing together different relay proteins involved in the same pathway.
Signal Termination
- Signal termination mechanisms are essential for maintaining homeostasis.
- The α subunit's GTPase activity hydrolyzes GTP to GDP, inactivating the G-protein.
- Phosphodiesterase converts cAMP to AMP, reducing the intracellular cAMP concentration.
- Phosphorylation of the receptor by a G-protein receptor kinase promotes the binding of β-arrestin, preventing further receptor activation.
- Protein phosphatases dephosphorylate target proteins, reversing their activation.
Cholera Toxin
- Vibrio cholerae bacteria secrete an enterotoxin that modifies the α subunit of the stimulatory G-protein, preventing GTP hydrolysis.
- This results in the permanent activation of the adenylyl cyclase pathway, leading to excessive cAMP production and severe watery diarrhea.
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