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Questions and Answers
What effect does the activated β/γ complex have on potassium channels?
What effect does the activated β/γ complex have on potassium channels?
What happens to the G protein after hydrolysis of its bound GTP?
What happens to the G protein after hydrolysis of its bound GTP?
What role do small intracellular signaling molecules play in signaling pathways?
What role do small intracellular signaling molecules play in signaling pathways?
How does epinephrine impact skeletal muscle cells according to the content?
How does epinephrine impact skeletal muscle cells according to the content?
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Which of the following correctly describes a sequence of events initiated by epinephrine?
Which of the following correctly describes a sequence of events initiated by epinephrine?
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What type of signals are required for a cell to survive?
What type of signals are required for a cell to survive?
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What happens to cells that do not receive the necessary signals for survival?
What happens to cells that do not receive the necessary signals for survival?
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Which of the following is NOT a requirement for cell proliferation/division?
Which of the following is NOT a requirement for cell proliferation/division?
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Which type of extracellular signals can lead to differentiation?
Which type of extracellular signals can lead to differentiation?
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What changes occur within cells due to extracellular signals acting slowly?
What changes occur within cells due to extracellular signals acting slowly?
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What role do intracellular signaling cascades play in cell function?
What role do intracellular signaling cascades play in cell function?
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Which cells require the appropriate signals to differentiate into specific types, such as nerve or bone cells?
Which cells require the appropriate signals to differentiate into specific types, such as nerve or bone cells?
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Which of these processes does NOT require changes in gene expression?
Which of these processes does NOT require changes in gene expression?
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What primarily limits most extracellular signal molecules from directly entering the cell?
What primarily limits most extracellular signal molecules from directly entering the cell?
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Which receptor types do small, hydrophobic extracellular signal molecules typically bind to?
Which receptor types do small, hydrophobic extracellular signal molecules typically bind to?
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Which of the following best explains why the same signal molecule can induce different responses in various cell types?
Which of the following best explains why the same signal molecule can induce different responses in various cell types?
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What is the role of acetylcholine in different target cells?
What is the role of acetylcholine in different target cells?
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How do extracellular signals typically regulate cellular behavior?
How do extracellular signals typically regulate cellular behavior?
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What kind of receptor do large hydrophilic extracellular signals predominantly bind to?
What kind of receptor do large hydrophilic extracellular signals predominantly bind to?
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Which outcome is NOT expected from extracellular signals binding to receptors?
Which outcome is NOT expected from extracellular signals binding to receptors?
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What do heart pacemaker cells primarily respond to in relation to acetylcholine?
What do heart pacemaker cells primarily respond to in relation to acetylcholine?
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Why might different cell types respond uniquely to the same neurotransmitter?
Why might different cell types respond uniquely to the same neurotransmitter?
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Which statement is true regarding the response of tissues to external signals?
Which statement is true regarding the response of tissues to external signals?
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What initiates the release of Ca2+ from the endoplasmic reticulum (ER)?
What initiates the release of Ca2+ from the endoplasmic reticulum (ER)?
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Which molecule acts as a second messenger in the signaling pathway described?
Which molecule acts as a second messenger in the signaling pathway described?
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What role do intracellular receptors play in cellular signaling?
What role do intracellular receptors play in cellular signaling?
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What effect does cross-linking have on Receptor Tyrosine Kinases (RTKs)?
What effect does cross-linking have on Receptor Tyrosine Kinases (RTKs)?
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Which type of receptor activates a G protein upon binding with a signaling molecule?
Which type of receptor activates a G protein upon binding with a signaling molecule?
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What role do calcium ions (Ca2+) play in the activation of protein kinase C (PKC)?
What role do calcium ions (Ca2+) play in the activation of protein kinase C (PKC)?
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What is the function of ion-channel-coupled receptors?
What is the function of ion-channel-coupled receptors?
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Which of the following is NOT a similarity between G Protein Coupled Receptors and Receptor Tyrosine Kinases?
Which of the following is NOT a similarity between G Protein Coupled Receptors and Receptor Tyrosine Kinases?
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What happens when a G-protein-coupled receptor is activated?
What happens when a G-protein-coupled receptor is activated?
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What is a characteristic feature of enzyme-coupled receptors?
What is a characteristic feature of enzyme-coupled receptors?
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Which of the following is an example of a channel that opens upon ligand binding?
Which of the following is an example of a channel that opens upon ligand binding?
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Which statement about cytoplasmic and nuclear receptors is incorrect?
Which statement about cytoplasmic and nuclear receptors is incorrect?
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What occurs when signaling molecules bind to receptors?
What occurs when signaling molecules bind to receptors?
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What is the primary role of protein kinase A (PKA) when activated by cAMP?
What is the primary role of protein kinase A (PKA) when activated by cAMP?
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Which molecule acts as a second messenger in many signaling pathways?
Which molecule acts as a second messenger in many signaling pathways?
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What initiates the production of Inositol 1,4,5-trisphosphate (IP3)?
What initiates the production of Inositol 1,4,5-trisphosphate (IP3)?
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The phosphorylation of which protein is crucial for the activation of glycogen phosphorylase?
The phosphorylation of which protein is crucial for the activation of glycogen phosphorylase?
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Which cellular process can be controlled by the signaling pathways involving cAMP?
Which cellular process can be controlled by the signaling pathways involving cAMP?
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Study Notes
Cell Signaling Overview
- Cells communicate via extracellular signal molecules
- Signals can act over long or short distances (endocrine, paracrine, neuronal, contact-dependent)
- A limited set of extracellular signals can produce a vast array of cellular behaviours
- Cells respond to signals in various ways, some fast, some slow, some involving gene expression and new protein synthesis.
- Cell surface receptors fall into three main classes: ion-channel coupled, G-protein coupled, and enzyme-coupled (e.g., receptor tyrosine kinases)
- Intracellular signaling molecules relay, amplify, integrate, distribute, and modulate signals via feedback.
Learning Objectives
- Contrast terms (endocrine, paracrine, autocrine) based on hormone release site and pathway to target tissue
- List two advantages of multistep pathways in cell signaling
- Describe signal amplification in target cells
- Explain how different cell types respond differently to the same signal molecule
- Describe how phosphorylation propagates signal information and how protein phosphatases turn off signal transduction pathways
- Define "second messenger" and briefly describe its role
- Describe how cytosolic Ca2+ concentration can be altered and how increased Ca2+ is involved in signal transduction
- Compare and contrast G-protein-linked, tyrosine-kinase and ligand-gated ion channels
- Explain how signals can be terminated
Signal Transduction
- Signal transduction is the conversion of one signal to another
- A target cell converts an external signal molecule into an internal signal
General Principles
- Signals can act over a long or short range.
- A limited number of extracellular signals can produce a wide variety of cell behaviors.
- Cell response to signals may be fast or slow.
- Cell-surface receptors relay extracellular signals via intracellular signaling pathways.
- Some intracellular signaling proteins act as molecular switches.
- Cell-surface receptors fall into three main categories: cascades and switches.
Animal Cell Communication
- Animals use extracellular signal molecules to communicate in various ways.
- Hormones from endocrine glands travel through the bloodstream for wide distribution.
- Paracrine signals act locally within a cell's neighbourhood
- Neuronal signals are transmitted electrically along nerve fibres (neurons). Release of neurotransmitters onto adjacent cells.
- In contact-dependent signaling, a cell-surface-bound signal molecule binds to a receptor protein on an adjacent cell.
Extracellular Signal Molecules
- Most extracellular signal molecules are large and hydrophilic, thus unable to cross the plasma membrane directly. They bind to cell-surface receptors, triggering intracellular signaling molecules.
- Some extracellular signal molecules (small, hydrophobic) can pass through the plasma membrane and bind to intracellular receptors, regulating gene transcription.
Same Signal, Different Responses
- Different cell types respond to the same signal molecule in varying ways.
- For example, acetylcholine has different effects on heart pacemaker cells, salivary gland cells, and skeletal muscle cells.
An Animal Cell Depends on Multiple Extracellular Signals
- Every cell type displays a set of receptor proteins enabling it to respond to a specific set of extracellular signal molecules.
- These molecules work in combinations to regulate cell behaviour.
- Cells may require multiple signals, e.g., for survival, growth, division, and differentiation, if deprived, cell death (apoptosis) may occur .
Extracellular Signals Can Act Rapidly or Slowly
- Certain cell responses, such as cell differentiation or increased growth/division, involve changes in gene expression. These occur relatively slowly.
- Other responses, such as cell movement or secretion, do not typically involve changes in gene expression; these occur more quickly.
Intracellular Signaling Pathways
- Cell surface receptor proteins activate one or more intracellular signaling pathways, a series of intracellular signaling molecules. They can be proteins or small molecules.
- Signaling molecules eventually interact with effector proteins to change cell behaviors (Metabolism, shape/movement, gene expression).
Intracellular Signaling Proteins
- A receptor protein on the cell surface transduces an extracellular signal into an intracellular signal, initiating intracellular signaling pathways.
- Many steps in the process can be modulated through feedback by other molecules.
- Some proteins are held in close proximity by scaffold proteins to increase speed, efficiency, and selectivity.
Feedback Regulation
- Protein Y increasing Protein T (positive feedback) can generate explosive responses.
- Protein Y inhibiting Protein T (negative feedback) can generate oscillations, similar to predator-prey relationships.
Molecular Switches
- Some proteins are activated/inhibited by addition or removal of a phosphate group.
- In one class, a protein kinase adds a phosphate group from ATP to the protein, which is then removed by protein phosphatase.
- In another class, a GTP-binding protein becomes active when it exchanges GDP for GTP; it switches off again by hydrolyzing GTP.
- The activity of monomeric GTPases is regulated by regulatory proteins.
Kinases
- Protein phosphorylation adds a phosphate group from ATP to proteins.
- Phosphate groups attach to serine, threonine, or tyrosine amino acid side chains.
- Several types of kinases exist, each targeting different proteins.
Lipid-Soluble vs Water-Soluble Ligands
- Lipid-soluble ligands can pass through the membrane to bind to intracellular receptors (e.g., hormones)
- Water-soluble ligands cannot enter the membrane. They bind to cell-surface receptors with signal molecule relay to the cytosol or inside the cell.
Intracellular Receptors
- Intracellular receptors: Cytoplasmic or nuclear
- Activated receptor-cortisol complex moves to the nucleus
- Binds to regulatory region of target gene and activates transcription.
Cell Surface Receptors
- Receptor categories: Ion Channel-Coupled, G-protein Coupled, Enzyme-Coupled (e.g., Receptor Tyrosine Kinases).
- Briefly described function of each type.
G-Protein Coupled Receptors (GPCRs)
- Describe the generalized function and structure.
- Mechanism of G-protein activation (GTP exchange)
- Mechanism of G-protein activation: ligand-binding -> GPCR conformation change -> G protein activation -> dissociation of alpha subunit with GDP -> exchange to GTP
- Effects of activated alpha-subunit, and of beta/gamma subunit.
- Signal termination (GTP hydrolysis).
Enzymes activated by G Proteins
- Activated enzymes increase the concentration of small intracellular signaling molecules, amplifying the signal.
- Second messengers diffuse and activate signaling proteins.
Cyclic AMP (cAMP)
- cAMP is a widely used second messenger.
- Adenylyl cyclase converts ATP to cAMP.
- cAMP activates protein kinase A (PKA).
- PKA phosphorylates other proteins, leading to a cellular response.
cAMP and Gene Transcription
- cAMP activates PKA that enters nucleus and phosphorylates proteins which causes transcription of genes.
Calcium Ions (Ca2+) and Inositol Triphosphate (IP3)
- Ca2+ acts as a second messenger in many pathways.
- Calcium regulation is crucial for cellular responses.
- Phospholipase C produces IP3 and DAG.
- IP3 triggers Ca2+ release from the ER.
Diacylglycerol (DAG)
- DAG remains in the plasma membrane.
- It, along with Ca2+, activates protein kinase C (PKC).
Enzyme-Coupled Receptors (RTKs)
- Describe general structure and function
- Mechanism of receptor activation: Signal binding ->dimerization ->cross-phosphorylation (tyrosine)
- Activation of downstream signaling pathways.
- Different types of proteins can bind to phosphorylated tyrosines.
Comparing GPCRs and RTKs
- Summarize the similarities and differences between the two receptor types.
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Description
Test your knowledge on the fundamentals of cell signaling, including types of signals and cell responses. This quiz will cover key concepts such as signal amplification, intracellular pathways, and the roles of different types of receptors. Perfect for students studying cell biology and related fields.
