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Questions and Answers
Which protein is primarily involved in regulating various proteins through calcium binding?
Which protein is primarily involved in regulating various proteins through calcium binding?
What is the main function of Rhodopsin in vision?
What is the main function of Rhodopsin in vision?
Which of the following pathways does Insulin receptor activation initiate?
Which of the following pathways does Insulin receptor activation initiate?
Gated ion channels respond to which of the following signals?
Gated ion channels respond to which of the following signals?
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What role does diacylglycerol play in PKC activation?
What role does diacylglycerol play in PKC activation?
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What is the primary feature of ionotropic receptors?
What is the primary feature of ionotropic receptors?
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Which protein is involved in stimulating the production of cAMP during olfaction?
Which protein is involved in stimulating the production of cAMP during olfaction?
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What mechanism allows for signal amplification in the MAPK cascade?
What mechanism allows for signal amplification in the MAPK cascade?
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What is the primary role of G proteins in signal transduction?
What is the primary role of G proteins in signal transduction?
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In the β-adrenergic receptor system, what is directly produced by the activation of adenylyl cyclase?
In the β-adrenergic receptor system, what is directly produced by the activation of adenylyl cyclase?
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Which feature of signal transduction allows the same signaling molecule to induce different responses in different cells?
Which feature of signal transduction allows the same signaling molecule to induce different responses in different cells?
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What term describes the ability of receptors to become unresponsive to persistent signals?
What term describes the ability of receptors to become unresponsive to persistent signals?
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Which molecules are known as second messengers in signal transduction pathways?
Which molecules are known as second messengers in signal transduction pathways?
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What principle of signal transduction explains the amplification of a signal?
What principle of signal transduction explains the amplification of a signal?
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Which characteristic ensures that only specific signals can bind to a receptor?
Which characteristic ensures that only specific signals can bind to a receptor?
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Which components play a critical role in the integration of multiple signals to produce a unified response?
Which components play a critical role in the integration of multiple signals to produce a unified response?
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What is the primary function of GTPase switches in signal transduction?
What is the primary function of GTPase switches in signal transduction?
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Which of the following correctly describes the action of phospholipase C (PLC)?
Which of the following correctly describes the action of phospholipase C (PLC)?
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How does desensitization affect receptor activity in signal transduction?
How does desensitization affect receptor activity in signal transduction?
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What is the effect of activating mutations in Gα proteins?
What is the effect of activating mutations in Gα proteins?
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Which mechanism is primarily responsible for the release of Ca²⁺ into the cytosol?
Which mechanism is primarily responsible for the release of Ca²⁺ into the cytosol?
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What role do adaptor proteins play in signal transduction?
What role do adaptor proteins play in signal transduction?
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What is a characteristic of receptor tyrosine kinases (RTKs)?
What is a characteristic of receptor tyrosine kinases (RTKs)?
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Which statement best describes second messengers such as diacylglycerol and IP3?
Which statement best describes second messengers such as diacylglycerol and IP3?
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Study Notes
Signal Transduction Overview
- Definition: The process of converting information into a chemical change
- Signal: Detected by specific receptors
- Conversion: Involves a chemical process to generate a cellular response
General Features of Signal Transduction
- Specificity: Achieved by molecular complementarity between signal and receptor molecules (non-covalent interactions)
- Sensitivity: High receptor affinity for ligands (Kd < 10⁻⁷ M)
- Amplification: Enzyme cascades amplify the signal
- Integration: System integrates multiple signals to produce a unified response
- Localization: Signaling components are confined to specific cellular structures for localized responses
Common Features of Signal Transduction
- Modularity: Proteins have multiple domains for recognizing features; scaffold proteins assemble interacting enzymes
- Desensitization: Receptors can become unresponsive to persistent signals
- Divergence: Signals often branch out for diverse responses
Types of Cellular Signals
- Cells respond to hormones, neurotransmitters, growth factors, nutrients, odorants, light, tastants, extracellular matrix components, and more
Basic Components of Signal Transduction
- Plasma membrane receptors (e.g., GPCRs)
- G proteins (bind GTP or GDP)
- Effector enzymes (e.g., adenylyl cyclase)
- Protein kinases and phosphatases
Steps in Signal Transduction
- Signal (ligand) binds receptor
- Activated receptor produces second messengers or protein activity changes
- Cellular response occurs
- Signal transduction ends
G Protein-Coupled Receptors (GPCRs)
- Definition: Largest family of plasma membrane receptors
- Components: Receptor with 7 transmembrane helices, G protein (active: GTP-bound, inactive: GDP-bound), effector enzyme or ion channel
- Mechanism: First messenger binds receptor → activates G protein → G protein activates effector enzyme → produces second messengers (e.g., cAMP)
- Second Messengers: Examples: cAMP, Ca²⁺, IP₃, diacylglycerol; regulate downstream signaling targets
β-Adrenergic Receptor System
- Ligand: Epinephrine binds to β-adrenergic receptors
- Pathway: GPCR activates G protein (Gs) → Gs activates adenylyl cyclase → produces cAMP → cAMP activates PKA (protein kinase A) → phosphorylates target proteins
- Termination: Decrease in epinephrine concentration, GTP hydrolysis by G protein, cAMP hydrolyzed to 5'-AMP by phosphodiesterase
Key Terms
- Agonist: Mimics natural ligand effects
- Antagonist: Blocks receptor activity
- GTPase Switch: G proteins deactivate by hydrolyzing GTP → GDP
- CREB: Transcription factor phosphorylated by PKA to regulate gene expression
Phospholipase C, IP₃, and Ca²⁺ Signaling
- Phospholipase C (PLC): Cleaves PIP₂ into diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP₃)
- DAG: Activates protein kinase C (PKC)
- IP₃: Releases Ca²⁺ from intracellular stores
- Ca²⁺: Acts as a second messenger
Defects in Signal Transduction
- Ras Mutations: Disrupt GTPase activity, leading to uncontrolled signaling and cancer
- Activating Mutations: Elevated cAMP levels (e.g., in adenomas)
- Inactivating Mutations: Impaired responses to hormonal signals
Regulation and Adaptation in Signal Transduction
- Desensitization: Receptors phosphorylated (e.g., by β-adrenergic receptor kinase); arrestin binding blocks G protein interaction
- Adaptor Proteins: Confine signaling molecules to specific regions (e.g., AKAPs)
Summary of Signal Transducers
- GPCRs: Coupled with G proteins, act via cAMP or other second messengers
- Receptor Tyrosine Kinases: Phosphorylate target proteins on Tyr residues
- Ligand-Gated Ion Channels: Direct ion flow
- Intracellular Receptors: Bind lipophilic signals (e.g., steroids)
Study Tip
- Focus on understanding the common themes in signal transduction: specificity, amplification, integration, modularity, and termination
Mutations in Gα Protein
- Activating Mutations: Lead to continuously elevated cAMP levels; found in ~40% of adenomas
- Inactivating Mutations: Cause unresponsiveness to hormones that use cAMP as a second messenger
Second Messengers: Diacylglycerol, IP₃, and Ca²⁺
- Phospholipase C (PLC): Cleaves PIP₂ (phosphatidylinositol 4,5-bisphosphate) into diacylglycerol and inositol 1,4,5-triphosphate (IP₃).
- Signals using PLC/IP₃/Ca²⁺ Pathway: Includes acetylcholine, gastrin-releasing peptide, angiotensin II, histamine, vasopressin, and oxytocin.
- Role of IP₃: Opens IP₃-gated Ca²⁺ channels in the ER, releasing Ca²⁺ into the cytosol.
- Activation of Protein Kinase C (PKC): Diacylglycerol and elevated Ca²⁺ levels activate PKC.
- Calcium as a Second Messenger: Cytosolic Ca²⁺ is tightly regulated by pumps and is elevated in response to stimuli; Calmodulin (CaM) binds Ca²⁺, changing conformation to regulate various proteins (e.g., CaM kinases)
G Protein-Coupled Receptors (GPCRs) in Vision, Olfaction, and Taste
- Vision: Rhodopsin (GPCR in rod cells) uses 11-cis-retinal as a chromophore; Rhodopsin Kinase and Arrestin desensitize activated rhodopsin
- Olfaction: Golf Protein triggers cAMP-gated ion channels, leading to action potentials
- Taste: Gustducin stimulates cAMP production and affects K⁺ channel phosphorylation
Common Features of GPCR Signaling
- Seven-transmembrane helices, intrinsic GTPase activity, cyclic nucleotides, and protein kinases are central to signaling.
- GPCRs are encoded in many species, including humans (~800 genes)
Receptor Tyrosine Kinases (RTKs)
- Structure: Extracellular ligand-binding domain and cytoplasmic tyrosine kinase domain
- Insulin Receptor Activation: Dimer of αβ monomers; autophosphorylation of Tyr residues activates kinase activity
- Signal Cascade: IRS1 binds phosphorylated Tyr residues; initiates signaling pathways
- PI3K activation leads to PIP₂ to PIP₃ conversion, GLUT4 translocation, and glycogen synthase activation
Ion Channels and Electrical Signaling
- Gated Ion Channels: Respond to ligands or voltage changes; regulate Na⁺, K⁺, Cl⁻, and Ca²⁺ flux
- Action Potentials: Generated by voltage-gated Na⁺ influx and K⁺ efflux, propagating electrical signals along neurons
- Receptor Channels: Ionotropic Receptors: Directly gated ion channels; metabotropic Receptors: Indirectly trigger second messenger pathways
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Description
Explore the essential concepts of signal transduction, including its definition and key features such as specificity, sensitivity, and amplification. Understand how signals are detected and processed within cells leading to appropriate responses. This quiz will cover common mechanisms and types involved in the signaling process.
