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Questions and Answers
Match the signal type to its distance traveled
Match the signal type to its distance traveled
Endocrine = Long distance signaling - usually carried by the bloodstream to its target Paracrine = Local signaling between cells Juxtacrine = Signal sent, received by adjacent cell Autocrine = Signal sent and received by the same cell
Which of the following is the correct order of the basic signaling events in cell signaling?
Which of the following is the correct order of the basic signaling events in cell signaling?
What are the first and second messengers in the epinephrine signaling pathway?
What are the first and second messengers in the epinephrine signaling pathway?
Epinephrine is the first messenger, and cAMP is the second Messenger.
Which of these options correctly describes the role of G proteins in cell signaling, specifically in relation to GPCRs?
Which of these options correctly describes the role of G proteins in cell signaling, specifically in relation to GPCRs?
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In the context of GPCRs, the binding of GTP to the G protein is the event that activates the G protein.
In the context of GPCRs, the binding of GTP to the G protein is the event that activates the G protein.
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What are the primary functions of protein kinases in cell signaling?
What are the primary functions of protein kinases in cell signaling?
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What is the role of phosphatases in cell signaling?
What is the role of phosphatases in cell signaling?
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What does a phosphorylation cascade refer to in cell signaling?
What does a phosphorylation cascade refer to in cell signaling?
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Calcium ions (Ca2+) can act as a second messenger in cell signaling.
Calcium ions (Ca2+) can act as a second messenger in cell signaling.
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What is the role of phospholipase C (PLC) in Ca2+ signaling?
What is the role of phospholipase C (PLC) in Ca2+ signaling?
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IP3 diffuses through the cytosol to bind with IP3-gated Ca2+ channels on the endoplasmic reticulum.
IP3 diffuses through the cytosol to bind with IP3-gated Ca2+ channels on the endoplasmic reticulum.
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The release of Ca2+ into the cytosol from the endoplasmic reticulum results in the activation of proteins, which then elicit cellular responses.
The release of Ca2+ into the cytosol from the endoplasmic reticulum results in the activation of proteins, which then elicit cellular responses.
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Which of the following options correctly describes a mechanism to stop or shut down a signaling cascade?
Which of the following options correctly describes a mechanism to stop or shut down a signaling cascade?
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What is receptor desensitization and why is it important in cell signaling?
What is receptor desensitization and why is it important in cell signaling?
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Study Notes
Cell Signaling Overview
- Cell signaling is the process by which cells communicate with each other.
- Extracellular signals are transmitted across the plasma membrane.
- Responses may include gene expression (nucleus, ribosomes, DNA, RNA, protein), release of calcium stored in ER, opening/closing of membrane transport proteins, etc.
Signal Classification by Distance
- Signals are classified by the distance they travel to their target.
- Endocrine signals: produced far from their site of action and carried by the bloodstream.
- Paracrine signals: produced and act locally.
- Juxtacrine signals: require physical contact between sending and receiving cells.
- Autocrine signals: produced by the same cell reacting to them.
Cell Signaling Steps
- Reception: Ligand binds specific receptor.
- Transduction: Signal transduction cascade transmits the reception signal involves a series of biochemical reactions often involving phosphorylation
- Response: Cellular response happens in a manner specific to cell type (examples are gene expression, activation/inactivation of protein or rearrangement of cytoskeleton)
Basic Steps in Cell Signaling(Diagram on page 5)
- Ligand binding (reception)
- Signal transduction (cascade)
- Cellular response
Receptors and Ligands
- Ligand: a messenger molecule that, binds receptors on the cell surface or intracellularly.
- Hydrophilic ligands bind cell surface receptors
- Hydrophobic ligands bind cytosolic receptors.
- Review: Hydrophilic molecules cannot pass through the hydrophobic cell membrane. Therefore, they need cell surface receptors to trigger intracellular pathways. Hydrophobic ligands are small and nonpolar. These molecules can pass through the cell membrane without the help of a surface receptor, therefore binding to cytosolic receptors.
Cell Surface Receptors vs Intracellular Receptors
- Cell surface receptors: bind hydrophilic ligands
- Intracellular receptors: bind hydrophobic ligands and small molecules, found in cytoplasm and nucleus
Step Two: Signal Transduction
- Transmission of a signal from a cell surface receptor to its target often involves a phosphorylation cascade.
- Phosphorylation usually activates a messenger.
- Kinases are enzymes that transfer phosphate groups to proteins.
- Some receptors have kinase activity of their own to start this process
- Receptor Tyrosine Kinases (RTKs)
Amplification of Signal
- A phosphorylation cascade involves many molecules phosphorylating each other to transmit the signal.
- Each step yields multiple phosphorylated products, so the input signal is amplified many times over.
- Signal amplification is like throwing a stone in a pond, creating many ripples from one initial disturbance.
Step Three: Response
- The cell's response depends on the cell type and the signal received. Responses may include turning genes on/off, activating or inactivating proteins (or rearranging cytoskeletons).
After the Response
- Cells need to stop responding to a signal, so that messengers can be reused.
- Kinases that activated the messengers are inactivated by phosphatases.
Shutting Down the Cascade (Diagram on page 12)
- Phosphatases remove phosphate groups from proteins, inactivating the cascade.
Second Messengers
- Not all players in signal transduction are phosphorylated proteins.
- First messenger: signaling molecule (ligand)
- Second messenger: small molecules produced in response to the first messenger, and can diffuse through the cell to transmit signals (examples are cAMP, IP3, Ca2+)
G Protein-Coupled Receptors (GPCRs)
- GPCRs are cell surface receptors that work together with G proteins to transmit signals.
- GPCRs transmit signals via various second messengers.
- GPCRs are transmembrane proteins and G proteins are lipid-anchored membrane proteins.
- GPCRs are a diverse group of receptors, with almost 1000 different GPCRs in humans.
- GPCRs—Inactive when GDP is bound, and Active when GTP is bound.
Ligand Binding to GPCR Causes G Protein Activation
- When a ligand binds to a GPCR, the GPCR changes shape, allowing the GPCR to bind to a G protein.
- Binding of the GPCR to the G protein causes the G protein to release GDP and bind to GTP.
- The binding of GTP activates the G protein.
Activated G proteins Initiate Signal Transduction
- Once the G protein (GTP) is activated, it can go on to activate or inhibit other proteins to transmit the signal.
GPCRs and Cyclic AMP (cAMP)
- Many GPCRs produce cAMP as a second messenger.
- Ligand→G protein→adenylyl cyclase→cAMP→protein kinase A(PKA).
- PKA then phosphorylates cellular proteins to respond.
cAMP as a Second Messenger
- cAMP is a second messenger used to send signals, activating kinase (PKA)
- Increased cAMP concentrations cause effects in different cells like breakdown of glycogen in skeletal muscle.
GPCR Signaling Cascade (Diagram on Page 20)
- Shows a simplified pathway from reception to transduction and response to a signal.
Protein Activation and Inactivation through GTP Hydrolysis
- G proteins turn themselves off by hydrolyzing GTP to GDP (using their own phosphatase).
Further Signaling: Calcium (Ca2+)
- Ca2+ is another second messenger in GPCR signaling.
- Intracellular Ca2+ is usually lower than extracellular Ca2+.
- ER and mitochondria store Ca2+.
- Increasing intracellular Ca2+ by releasing it from the ER or mitochondria causes cellular response, as ca2+ activates various proteins.
Question 1: Match Signal Type to Distance Traveled (page 4)
- Endocrine: Long distance signaling
- Paracrine: Local signaling
- Juxtacrine: Signal sent and received by adjacent cell
- Autocrine: Signal sent and received by the same cell
Question 2: Cell Signaling Steps in Order (page 13)
- Ligand binds receptor
- Signal transduction
- Response
- Turn off signal
Question 3: First and Second Messengers (page 22)
- In the GPCR pathway, the first messenger is the ligand, and the second messenger is cAMP.
Question 4: GPCR-Related Signaling Events in Order (page 27)
- First messenger binds GPCR
- G protein docks with GPCR
- G protein exchanges GDP for GTP
- G protein activates an enzyme producing a second messenger
- Second messenger production triggers a response.
Stopping Cell Signaling (page 28)
- Receptor-ligand interactions are reversible, and normally, a specific amount of receptor-ligand complexes must combine .
- Signal is usually initiated by a change in ligand concentration.
- Reducing the availability of ligands stops the signaling process.
- Desensitization occurs from prolonged ligand binding, which reduces receptors.
- Cells can dynamically adjust their sensitivity to ligands.
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Description
This quiz explores the fundamental concepts of cell signaling, including how cells communicate with each other through various signals. You will learn about the classification of signals based on their traveling distance and the essential steps involved in the signaling process. Test your understanding of key terms and processes involved in cell signaling.
