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Questions and Answers

What is the primary purpose of cell signaling?

  • To enhance cellular membrane stability
  • To respond to external stimuli (correct)
  • To facilitate intracellular respiration
  • To regulate DNA replication
  • Which type of signaling involves a cell sending messages to itself?

  • Endocrine signaling
  • Autocrine signaling (correct)
  • Neurocrine signaling
  • Paracrine signaling
  • How do ligand molecules primarily interact with cells?

  • They alter the cell's genetic material directly
  • They bind to cell-surface receptors (correct)
  • They rearrange the cell's structural proteins
  • They penetrate the nucleus to initiate transcription
  • What occurs when a receptor undergoes a conformational change?

    <p>It transmits the message into the cytoplasmic domain (B)</p> Signup and view all the answers

    What is a characteristic of endocrine signaling?

    <p>It transmits signals through the bloodstream (A)</p> Signup and view all the answers

    What is generated as part of signal transduction to facilitate intracellular communication?

    <p>Second messengers (B)</p> Signup and view all the answers

    Which of the following molecules can serve as ligands in cell signaling?

    <p>Steroids and neurotransmitters (C)</p> Signup and view all the answers

    What role does arrestin play in the desensitization of G protein-coupled receptors (GPCRs)?

    <p>Inhibits G protein binding and promotes internalization (D)</p> Signup and view all the answers

    How does Gα subunit inactivate itself during signal transduction?

    <p>By slowly hydrolyzing GTP (C)</p> Signup and view all the answers

    Which of the following describes a function of cyclic adenosine monophosphate (cAMP)?

    <p>Activate calcium channels (D)</p> Signup and view all the answers

    What is the primary function of Protein Kinase A when activated by cAMP?

    <p>It phosphorylates various substrates (A)</p> Signup and view all the answers

    What effect do Regulators of G protein Signaling (RGSs) have on G protein signaling?

    <p>Accelerate the rate of GTP hydrolysis (D)</p> Signup and view all the answers

    What occurs when a ligand binds to the extracellular domain of a receptor?

    <p>Alters receptor conformation (C)</p> Signup and view all the answers

    Which molecule is exchanged for GDP upon G protein activation?

    <p>GTP (D)</p> Signup and view all the answers

    What is the result of GTP binding to the Gα subunit?

    <p>Dissociation from Gßγ subunits (A)</p> Signup and view all the answers

    What second messenger is produced by adenylyl cyclase?

    <p>cAMP (B)</p> Signup and view all the answers

    How does the Gα subunit return to its inactive state?

    <p>Through hydrolysis of GTP (C)</p> Signup and view all the answers

    What happens to the affinity of Gα for effector proteins after GTP hydrolysis?

    <p>Decreases affinity for effectors (B)</p> Signup and view all the answers

    What is the role of G protein-coupled receptor kinase (GRK) in desensitization?

    <p>Receptor phosphorylation (A)</p> Signup and view all the answers

    What effect does arrestin have on G protein-coupled receptors?

    <p>It inhibits further G protein binding (B)</p> Signup and view all the answers

    What happens to desensitized receptors after they are dephosphorylated?

    <p>They are returned to the cell membrane (A)</p> Signup and view all the answers

    What is the primary action of phospholipase C in the signaling pathway?

    <p>Hydrolyze membrane phospholipids (B)</p> Signup and view all the answers

    What is the main function of G protein-coupled receptors (GPCRs)?

    <p>Trigger second messengers in signal transduction (D)</p> Signup and view all the answers

    Which of the following correctly describes the structure of GPCRs?

    <p>7 transmembrane helical domains (B)</p> Signup and view all the answers

    What happens upon ligand binding to a GPCR?

    <p>Conformational change of the receptor (B)</p> Signup and view all the answers

    What occurs after GDP is exchanged for GTP in G proteins?

    <p>Gα subunit dissociates and binds to effector (C)</p> Signup and view all the answers

    Which of the following is NOT a type of molecule that GPCRs interact with?

    <p>Carbohydrates (B)</p> Signup and view all the answers

    What is the role of GTP in G protein signaling?

    <p>It activates the G protein (A)</p> Signup and view all the answers

    Which effector protein is associated with the conversion of ATP to cAMP?

    <p>Adenylyl cyclase (C)</p> Signup and view all the answers

    What characterizes the heterotrimeric G protein?

    <p>It is composed of α, ß, and γ subunits (C)</p> Signup and view all the answers

    How does Gα affect the activity of effector proteins?

    <p>It can activate or inhibit effector proteins (D)</p> Signup and view all the answers

    What happens during the hydrolysis of GTP in the Gα subunit?

    <p>GTP is converted into GDP and Pi (C)</p> Signup and view all the answers

    What results from the conformational change of Gα?

    <p>Increased affinity for Gβγ subunits (A)</p> Signup and view all the answers

    Which protein binds to the receptor during the second step of desensitization?

    <p>Arrestin (B)</p> Signup and view all the answers

    Which process does Arrestin promote?

    <p>Internalization of GPCRs (B)</p> Signup and view all the answers

    What occurs after Arrestin binds to the GPCR?

    <p>G protein binding is inhibited (C)</p> Signup and view all the answers

    What happens to GPCRs after internalization?

    <p>They are dephosphorylated and returned to the membrane (D)</p> Signup and view all the answers

    What does the hydrolysis of GTP by Gα indicate?

    <p>Termination of the G protein's action (C)</p> Signup and view all the answers

    How does phosphorylation of the receptor affect G protein binding?

    <p>It reduces G protein binding (D)</p> Signup and view all the answers

    What is one of the main roles of Gβγ subunits after Gα is activated?

    <p>To modulate effector proteins (C)</p> Signup and view all the answers

    Which of the following is a result of protein phosphorylation?

    <p>Activation of metabolic enzymes (B)</p> Signup and view all the answers

    In which of the following ways can phosphorylation affect protein behavior?

    <p>It can alter the protein's subcellular location. (A)</p> Signup and view all the answers

    Which type of receptor is NOT included in the major receptor types listed?

    <p>Peptide hormone receptors (A)</p> Signup and view all the answers

    What is one of the roles of kinases in cellular signaling?

    <p>They add phosphate groups to target proteins. (D)</p> Signup and view all the answers

    How do different cell types exhibit variability in protein phosphorylation?

    <p>Due to differences in phospho patterns. (B)</p> Signup and view all the answers

    Which amino acids are primarily involved in protein phosphorylation?

    <p>Serine, threonine, tyrosine (A)</p> Signup and view all the answers

    Which statement best describes a function of signaling pathways?

    <p>They mediate responses leading to alterations in cell activities. (A)</p> Signup and view all the answers

    What is the role of epinephrine in glucose regulation?

    <p>Activates adrenergic GPCR in the liver to stimulate glucose release (D)</p> Signup and view all the answers

    Which subunit is activated by ß-adrenergic receptors in cardiac muscle cells?

    <p>Gs subunit (C)</p> Signup and view all the answers

    What effect do beta blockers have on the cardiovascular system?

    <p>Decrease heart rate and force of contraction (D)</p> Signup and view all the answers

    What is the main function of glucagon in blood glucose regulation?

    <p>Activates cAMP production in liver cells (A)</p> Signup and view all the answers

    How does the activation of the Gi subunit affect intestinal smooth muscle cells?

    <p>Inhibits cAMP production (A)</p> Signup and view all the answers

    What initiates the conformational change in a G protein-coupled receptor (GPCR)?

    <p>Binding of a ligand to the receptor (D)</p> Signup and view all the answers

    Which component is primarily responsible for activating the effector protein in GPCR signaling?

    <p>GTP-Gα subunit (A)</p> Signup and view all the answers

    What is the role of phospholipase C in GPCR signaling?

    <p>Convert PIP2 into inositol trisphosphate and diacylglycerol (C)</p> Signup and view all the answers

    What type of second messenger is generated by adenylyl cyclase?

    <p>cAMP (D)</p> Signup and view all the answers

    Which part of a G protein is responsible for its activation upon ligand binding to a GPCR?

    <p>Gα subunit (A)</p> Signup and view all the answers

    What effect is caused by the hydrolysis of GTP on the Gα subunit?

    <p>Returns Gα to inactive state (C)</p> Signup and view all the answers

    Which of the following molecules is NOT typically a ligand for G protein-coupled receptors?

    <p>Glucose (B)</p> Signup and view all the answers

    Which of the following is a component of a heterotrimeric G protein?

    <p>Three subunits Gα, Gβ, and Gγ (D)</p> Signup and view all the answers

    What is the main action of Gβγ subunits after Gα activation?

    <p>Regulates other effectors (B)</p> Signup and view all the answers

    What occurs after the Gα subunit hydrolyzes GTP to GDP?

    <p>It increases affinity for Gβγ subunits. (C)</p> Signup and view all the answers

    What is the primary function of arrestin in the context of GPCRs?

    <p>It binds to the receptor and inhibits G protein binding. (D)</p> Signup and view all the answers

    Which of the following processes occurs during the desensitization of GPCRs?

    <p>Phosphorylation of the receptor by GRK. (A)</p> Signup and view all the answers

    What happens to GPCRs once they are internalized?

    <p>They can be dephosphorylated and recycled back to the membrane. (C)</p> Signup and view all the answers

    Which of the following statements is true regarding the conformational change of Gα?

    <p>It reduces the affinity for effector proteins while increasing affinity for Gβγ. (A)</p> Signup and view all the answers

    What role does hydrolysis of GTP play in G protein signaling?

    <p>It inactivates the Gα subunit and stops the signal. (A)</p> Signup and view all the answers

    Which kinase is responsible for the phosphorylation of GPCRs during desensitization?

    <p>G Protein-Coupled Receptor Kinase (GRK) (A)</p> Signup and view all the answers

    What is the effect of receptor phosphorylation in terms of G protein binding?

    <p>It inhibits G protein binding. (B)</p> Signup and view all the answers

    Which of the following describes the outcome of Gα binding GTP?

    <p>It activates the Gα subunit. (C)</p> Signup and view all the answers

    What occurs when arrestin binds to a GPCR?

    <p>It inhibits interaction with G proteins. (B)</p> Signup and view all the answers

    What is a consequence of GTP hydrolysis by the Gα subunit?

    <p>It leads to the inactivation of the Gα subunit. (A)</p> Signup and view all the answers

    Which second messenger is a result of adenylyl cyclase activity when stimulated by the Gs subunit?

    <p>Cyclic adenosine monophosphate (cAMP) (C)</p> Signup and view all the answers

    What occurs to GPCRs after they undergo internalization?

    <p>They are recycled back to the cell membrane. (D)</p> Signup and view all the answers

    Which statement correctly describes the role of protein kinases activated by cAMP?

    <p>They can activate glycogen synthesis pathways. (C)</p> Signup and view all the answers

    What is the function of Protein Kinase A Anchoring Proteins (AKAPs)?

    <p>They organize and stabilize PKA interactions at specific cellular locations. (C)</p> Signup and view all the answers

    How do Regulators of G protein Signaling (RGSs) alter G protein signaling?

    <p>They accelerate the rate of GTP hydrolysis by Gα. (A)</p> Signup and view all the answers

    What metabolic effects are associated with elevated levels of cAMP in cells?

    <p>Stimulated breakdown of glycogen and enhanced glucose regulation. (C)</p> Signup and view all the answers

    What role does arrestin play in G protein-coupled receptor signaling?

    <p>It promotes internalization and desensitization of the receptor. (B)</p> Signup and view all the answers

    What is the primary consequence of excessive activation of G12/13 proteins?

    <p>Induction of cell proliferation and potential malignancies. (C)</p> Signup and view all the answers

    Which of the following is NOT considered a common second messenger involved in GPCR signaling?

    <p>Glucose (C)</p> Signup and view all the answers

    What is the primary consequence of activating the ß-adrenergic receptor in cardiac muscle cells?

    <p>Increased rate and force of contraction (A)</p> Signup and view all the answers

    How does the α-adrenergic receptor affect intestinal smooth muscle cells?

    <p>It activates Gi subunit to inhibit cAMP production (C)</p> Signup and view all the answers

    Which hormone is released from the pancreas in response to low glucose levels?

    <p>Glucagon (C)</p> Signup and view all the answers

    What mechanism do beta blockers utilize to lower blood pressure?

    <p>Blocking the effects of epinephrine (C)</p> Signup and view all the answers

    What is a key difference between autocrine and paracrine signaling?

    <p>Autocrine signaling involves receptors on the same cell, while paracrine signaling involves nearby cells. (C)</p> Signup and view all the answers

    What effect does cAMP have on glucose mobilization from the liver?

    <p>It promotes glycogen breakdown. (B)</p> Signup and view all the answers

    Which route of message transmission generates second messengers through an effector enzyme?

    <p>Signal transduction (D)</p> Signup and view all the answers

    What type of molecules can act as ligands in cell signaling?

    <p>Lipids, proteins, and vitamins (D)</p> Signup and view all the answers

    In the context of signal transduction, what is the role of an effector enzyme?

    <p>It generates second messengers. (C)</p> Signup and view all the answers

    What mechanism allows receptor proteins to relay messages into the cytoplasmic domain?

    <p>Conformational change of the receptor (D)</p> Signup and view all the answers

    Which cell signaling type involves messenger molecules that travel long distances in the bloodstream?

    <p>Endocrine signaling (D)</p> Signup and view all the answers

    What is the first event that typically occurs when a ligand binds to its receptor?

    <p>The receptor undergoes a conformational change. (A)</p> Signup and view all the answers

    What happens to Gα subunit when it undergoes hydrolysis of GTP?

    <p>It converts GTP to GDP and Pi. (D)</p> Signup and view all the answers

    How does the conformational change of Gα affect its interaction with other proteins?

    <p>Decreases affinity for effector proteins and increases affinity for Gβγ subunits. (D)</p> Signup and view all the answers

    Which of the following statements correctly describes the role of the Gα subunit after GDP is exchanged for GTP?

    <p>Gα dissociates from Gßγ and binds to an effector protein. (C)</p> Signup and view all the answers

    What is the function of G protein-coupled receptor kinase (GRK) in receptor desensitization?

    <p>It phosphorylates the receptor. (A)</p> Signup and view all the answers

    What role does arrestin play in the process of GPCR desensitization?

    <p>It promotes receptor internalization. (C)</p> Signup and view all the answers

    What is the consequence of GTP hydrolysis by the Gα subunit in the signaling pathway?

    <p>Gα reverts to its GDP-bound state, decreasing effector affinity. (C)</p> Signup and view all the answers

    Which of the following best describes what happens after a receptor is phosphorylated by GRK?

    <p>The receptor is internalized and tagged for degradation. (C)</p> Signup and view all the answers

    How does the binding of arrestin affect G protein-coupled receptors (GPCRs)?

    <p>It promotes receptor desensitization and internalization. (B)</p> Signup and view all the answers

    What occurs to GPCRs after they are desensitized and dephosphorylated?

    <p>They are returned to the cell membrane and resensitized. (D)</p> Signup and view all the answers

    What role does adenylyl cyclase play in the signaling pathway activated by GPCRs?

    <p>It converts ATP to cAMP, serving as a second messenger. (B)</p> Signup and view all the answers

    What effect does the affinity change of Gα subunit have on its interaction with effector proteins?

    <p>It decreases the effectiveness of signal transduction. (C)</p> Signup and view all the answers

    What happens to GPCRs during the desensitization process after receptor phosphorylation?

    <p>They are marked for recycling back to the membrane. (C)</p> Signup and view all the answers

    Which of the following correctly describes the change in affinity of Gα for its targets after GTP hydrolysis?

    <p>Gα decreases its affinity for both effector proteins and Gßγ subunits. (A)</p> Signup and view all the answers

    What is a consequence of the Gα subunit's hydrolysis of GTP in relation to G protein signaling?

    <p>Deactivation of Gα, thus stopping the signal. (D)</p> Signup and view all the answers

    Which of the following describes the mechanism by which Gα subunit can return to its inactive state?

    <p>By hydrolyzing GTP into GDP and Pi. (D)</p> Signup and view all the answers

    Which statement accurately reflects the role of Gβγ subunits after the activation of Gα?

    <p>They can activate their own signaling pathways independently. (B)</p> Signup and view all the answers

    Which process is promoted by the binding of arrestin to a GPCR?

    <p>Preparation of the receptor for degradation. (B)</p> Signup and view all the answers

    What physiological role does GTP-Gα play after its activation?

    <p>Activates or inhibits effector proteins. (A)</p> Signup and view all the answers

    How does the binding of a ligand to the extracellular domain of a GPCR influence the receptor?

    <p>It alters the receptor conformation, increasing G protein affinity. (A)</p> Signup and view all the answers

    What is the consequence of excessive activation of G12/13 proteins?

    <p>Cell proliferation and potential malignancies (B)</p> Signup and view all the answers

    How does Protein Kinase A (PKA) become activated in response to cAMP levels?

    <p>Binding of cAMP to regulatory subunits (D)</p> Signup and view all the answers

    What is one of the main functions of second messengers in cellular signaling?

    <p>Amplification of the signal response (A)</p> Signup and view all the answers

    Which process is triggered by the activation of adenylyl cyclase?

    <p>Increase in intracellular cAMP levels (C)</p> Signup and view all the answers

    What is a primary effect of phospholipase C (PLC) when activated by Gq proteins?

    <p>Produces inositol trisphosphate (IP3) and diacylglycerol (DAG) (A)</p> Signup and view all the answers

    What regulates the strength and duration of the signaling response in G protein-coupled receptors?

    <p>Hydrolysis rate of GTP by Gα subunit (D)</p> Signup and view all the answers

    What signal cascade is initiated when Gs proteins activate adenylate cyclase?

    <p>Formation of cyclic nucleotides (D)</p> Signup and view all the answers

    What happens to GPCRs after they are internalized following desensitization?

    <p>They undergo dephosphorylation and can be resensitized (A)</p> Signup and view all the answers

    Which molecule is produced when cAMP activates Protein Kinase A (PKA)?

    <p>Phosphorylated proteins (C)</p> Signup and view all the answers

    Flashcards

    Cell Signaling

    The process by which cells respond to external stimuli for survival.

    Ligand

    An extracellular signal molecule, such as hormones or neurotransmitters.

    Receptor

    A protein on the target cell that receives the signal (ligand).

    Autocrine Signaling

    A cell signals itself, sending and responding to its own messenger.

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    Paracrine Signaling

    Local signaling between adjacent cells; messages travel short distances.

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    Endocrine Signaling

    Long-distance signaling, where hormones travel through the bloodstream to reach target tissues.

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    Signal Transduction

    The process where a signal is relayed inside a cell to trigger an action.

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    G protein-coupled receptor (GPCR)

    A large family of membrane proteins that are important in cell signaling.

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    7 transmembrane helical domains

    A structural feature of GPCRs, consisting of seven alpha-helices that pass through the cell membrane.

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    Heterotrimeric G protein

    A protein complex that relays signals from a GPCR to an effector molecule.

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    GDP-GTP exchange

    The process where GDP is replaced by GTP in the G protein alpha subunit, initiating signal transduction.

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    effector

    An enzyme or protein that carries out a specific cellular response after receiving a signal from the G protein.

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    Adenylyl cyclase

    An enzyme that converts ATP into cyclic AMP (cAMP).

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    Second messenger (cAMP)

    A small molecule that relays a signal from a GPCR to target proteins inside the cell.

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    Ligand binding

    The process where a signaling molecule (ligand) binds to a receptor activating it.

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    Arrestin protein

    A protein that binds to an activated GPCR, inhibiting the interaction with G proteins and promoting receptor internalization.

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    Regulators of G protein Signaling (RGSs)

    Proteins that speed up the GTP hydrolysis by the Gα subunit, leading to a faster termination of the signal.

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    What are second messengers?

    Small molecules that relay signals from GPCRs to intracellular targets, amplifying the initial signal.

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    cAMP

    A common second messenger that activates protein kinases, leading to various cellular responses.

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    Protein Kinase A (PKA)

    An enzyme activated by cAMP, which phosphorylates target proteins, leading to changes in cell function.

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    G Protein Activation

    The G protein alpha subunit (Gα) undergoes a conformational change, exchanging GDP for GTP, activating the protein.

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    Effector Protein

    A protein, often an enzyme, that is activated or inhibited by the GTP-bound Gα subunit, leading to downstream effects within the cell.

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    Adenylyl Cyclase: What does it do?

    A common effector protein that converts ATP to cAMP (cyclic AMP), a second messenger that amplifies and relays the signal.

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    G Protein-Coupled Receptor (GPCR) Desensitization

    The process of reducing the sensitivity of GPCRs by phosphorylation, which prevents further activation of G proteins.

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    Internalization of GPCRs

    The process by which GPCRs are removed from the cell surface and transported into the cell's interior.

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    Dephosphorylation of GPCRs

    The removal of phosphate groups from phosphorylated GPCRs, allowing them to be re-sensitized and re-inserted into the cell membrane.

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    Gα Subunit Self-Deactivation

    The GTP-bound Gα subunit, after activating the effector protein, hydrolyzes GTP back to GDP, deactivating itself.

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    Gα Affinity for Gßγ

    When Gα is bound to GTP, its affinity for the Gßγ subunits is low. Upon GTP hydrolysis, its affinity for Gßγ increases, leading to re-association.

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    How do ligands affect GPCRs?

    Ligands bind to the extracellular domain of GPCRs, triggering a conformational change that increases the receptor's affinity for G proteins.

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    Gα subunit off switch

    The Gα subunit deactivates itself by hydrolyzing GTP into GDP and inorganic phosphate (Pi).

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    Gα conformational change

    When Gα hydrolyzes GTP, it undergoes a conformational change, reducing its affinity for effector proteins and increasing its affinity for Gβγ subunits.

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    Desensitization

    A process that reduces a receptor's responsiveness to a signal.

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    GRK

    G protein-coupled receptor kinase, an enzyme that phosphorylates GPCRs.

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    Arrestin

    A protein that binds to phosphorylated GPCRs, preventing G protein binding and promoting internalization of the receptor.

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    Degradation

    The breakdown of a protein into smaller components.

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    Dephosphorylation

    Removal of phosphate groups from a protein.

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    Re-sensitization

    A process where a GPCR is restored to its active state, ready to receive signals again.

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    G Protein-Coupled Receptors

    A large family of cell surface receptors that work with G proteins to relay signals.

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    Kinase

    An enzyme that adds a phosphate group (Pi) to a protein, often activating or inactivating it.

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    Phosphatase

    An enzyme that removes a phosphate group (Pi) from a protein, often deactivating or reactivating it.

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    G-protein Coupled Receptors (GPCRs)

    A large family of cell surface receptors that bind signaling molecules and activate G proteins to relay signals.

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    RTKs (Receptor Protein-Tyrosine Kinases)

    A type of cell surface receptor that binds signaling molecules and activates itself by phosphorylation, triggering a cascade of intracellular events.

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    Ligand-Gated Channels

    Membrane proteins that open or close a channel in response to binding a specific signaling molecule.

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    Steroid Hormone Receptors

    Nuclear receptors that bind steroid hormones and regulate gene expression.

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    Gα Subunit Deactivation

    The Gα subunit, after activating an effector protein, hydrolyzes GTP back to GDP, turning itself off.

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    Desensitization of GPCRs

    The process of reducing a receptor's responsiveness to a signal, often by phosphorylation.

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    G Protein-Coupled Receptor Kinase (GRK)

    An enzyme that adds phosphate groups to GPCRs, thus desensitizing them.

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    Arrestin: GPCR Inhibitor

    A protein that binds to phosphorylated GPCRs, preventing G protein attachment and promoting receptor internalization.

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    Dephosphorylation: Re-sensitization

    The removal of phosphate groups from a GPCR, allowing it to return to the cell membrane and become sensitive again.

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    Gα Affinity for Gßγ Subunits

    When bound to GTP, Gα has a low affinity for Gßγ subunits. But after GTP hydrolysis, the affinity for Gßγ increases, allowing them to re-associate.

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    What is a second messenger in GPCR signaling?

    A small intracellular molecule, like cAMP, that relays and amplifies the signal from a GPCR to target proteins inside the cell.

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    Arrestin: What does it do?

    Arrestin is a protein that binds to an activated GPCR, inhibiting binding of G protein, and promoting internalization of the receptor.

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    G Protein-Coupled Receptors: Desensitization

    Desensitization is a process that reduces the responsiveness of a GPCR to a stimulus. It occurs when Arrestin binds, stopping the receptor from interacting with G proteins.

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    G Protein-Coupled Receptors: Internalization

    Internalization is the process of removing a GPCR from the cell surface and transporting it to the interior of the cell.

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    RGS: Regulators of G protein Signaling

    RGS proteins accelerate the rate of GTP hydrolysis by the Gα subunit, leading to a faster termination of the signal.

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    cAMP: What is it?

    cAMP, or cyclic adenosine monophosphate, is a common second messenger that is produced by adenylyl cyclase and activates protein kinases.

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    Effectors: How are they activated?

    Effectors in GPCR signaling are proteins, often enzymes, that are activated or inhibited by the GTP-bound Gα subunit, leading to downstream effects.

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    What are GPCRs?

    G protein-coupled receptors (GPCRs) are a large family of membrane proteins that bind signaling molecules and activate G proteins to relay signals within cells. They are involved in a wide range of cellular processes, including sensory perception, neurotransmission, and hormone signaling.

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    How do the 7 transmembrane helices of GPCRs affect their function?

    The 7 transmembrane helices of GPCRs form a structure that spans the cell membrane. The extracellular domain binds signaling molecules (ligands), and the intracellular domain interacts with G proteins. This arrangement enables the receptor to relay signals across the membrane.

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    What are G proteins, and what are their subunits?

    G proteins are proteins that relay signals from GPCRs to effector proteins within the cell. They are made up of three subunits: Gα (alpha), Gß (beta), and Gγ (gamma). The Gα subunit is responsible for binding GTP and interacting with effector proteins.

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    How does ligand binding activate G proteins?

    When a ligand binds to a GPCR, it triggers a conformational change in the receptor. This change increases the receptor's affinity for G proteins. The Gα subunit of the G protein then exchanges GDP for GTP, becoming activated.

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    How does the activated G protein interact with effector proteins?

    Once activated, the GTP-bound Gα subunit dissociates from the Gßγ dimer and binds to effector proteins. This interaction either activates or inhibits the effector protein, leading to a cellular response.

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    What are some examples of effector proteins?

    Effector proteins are enzymes or other proteins that carry out specific cellular responses after receiving a signal from the G protein. Examples include adenylyl cyclase, phospholipase C, and cGMP phosphodiesterase.

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    What is the role of GTP hydrolysis in the G protein cycle?

    GTP hydrolysis is the process by which the Gα subunit converts GTP back to GDP. This deactivates the G protein, ending the signal transduction pathway.

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    What are some examples of second messengers?

    Important second messengers include cyclic AMP (cAMP), cyclic GMP (cGMP), inositol triphosphate (IP3), and diacylglycerol (DAG). Each second messenger has specific targets and functions within the cell.

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    What are α- and β- adrenergic receptors?

    They are different types of G protein-coupled receptors (GPCRs) that bind to epinephrine (adrenaline). These receptors are involved in the "fight-or-flight" response, but they trigger different effects depending on the tissue.

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    How does epinephrine affect heart muscle?

    Epinephrine binds to β-adrenergic receptors on heart muscle cells, activating the Gs subunit of the G protein. This stimulates cAMP production, causing the heart to beat faster and with more force.

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    How does epinephrine affect intestinal smooth muscle?

    Epinephrine binds to α-adrenergic receptors on intestinal smooth muscle, activating the Gi subunit. This inhibits cAMP production, leading to muscle relaxation.

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    What is a Beta Blocker?

    Beta blockers are medications that block the effects of epinephrine on β-adrenergic receptors, which helps lower blood pressure.

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    How does glucagon regulate blood glucose?

    Glucagon, a hormone released by the pancreas when blood glucose is low, activates a GPCR in the liver. This stimulates the breakdown of glycogen and the release of glucose into the bloodstream, raising blood sugar levels.

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    Second Messengers

    Small molecules generated inside a cell to amplify and transmit the signal from a receptor.

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    cAMP (Cyclic AMP)

    A common second messenger that activates protein kinases, leading to various cellular responses.

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    GPCR activation

    A ligand binds to the extracellular domain of a GPCR, causing a conformational change in the receptor that increases its affinity for G proteins.

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    What does GTP-Gα do?

    The activated Gα subunit detaches from the other parts of the G protein and binds to an effector protein, activating or inhibiting it.

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    How does Gα deactivate?

    The Gα subunit hydrolyzes GTP back to GDP, returning to its inactive state.

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    How does a receptor become desensitized?

    A G protein-coupled receptor kinase (GRK) phosphorylates the receptor, reducing its sensitivity to further stimulation.

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    What does Arrestin do?

    Arrestin binds to a phosphorylated GPCR, blocking G protein interaction and promoting receptor internalization.

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    What happens to internalized GPCRs?

    Internalized GPCRs can be:

    • Used for internal signaling.
    • Degraded.
    • Dephosphorylated and returned to the membrane for re-sensitization.
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    What are effectors?

    Effector proteins are the targets of activated Gα subunits. They carry out specific cellular responses depending on the signal received.

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    What are examples of effectors?

    Examples of effectors include adenylyl cyclase, phospholipase C, and cGMP phosphodiesterase.

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    Gα Deactivation

    The Gα subunit switches itself off by hydrolyzing GTP back to GDP and inorganic phosphate (Pi).

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    GPCR Desensitization

    The process of reducing a receptor's responsiveness to a signal. This often occurs when the receptor is phosphorylated.

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    GRK: G Protein-Coupled Receptor Kinase

    An enzyme that adds phosphate groups to GPCRs, leading to desensitization.

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    Second Messenger in GPCR Signaling

    A small intracellular molecule, like cAMP, that amplifies and relays the signal from a GPCR to target proteins inside the cell.

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    Arrestin: What's its role?

    Arrestin is a protein that binds to activated GPCRs. It prevents further G protein activation and promotes internalization of the receptor, effectively stopping the signal.

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    Norepinephrine (Noradrenaline)

    A neurotransmitter and hormone that plays a crucial role in the 'fight-or-flight' response, stimulating the sympathetic nervous system. It's released from the adrenal glands and nerve endings.

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    Epinephrine (Adrenaline)

    A hormone secreted by the adrenal glands that prepares the body for immediate action. It's part of the 'fight-or-flight' response, causing heart rate, blood pressure, and blood sugar levels to increase.

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    What are β-Adrenergic Receptors?

    These are G protein-coupled receptors (GPCRs) that bind to epinephrine (adrenaline). They're found on various tissues, causing different effects, like increasing heart rate and relaxing intestinal muscles.

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    What are Beta Blockers?

    These are medications that block the effects of epinephrine on β-adrenergic receptors, which helps lower blood pressure. They reduce the heart's rate and force of contraction.

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    Study Notes

    Molecular Mechanisms of Disease - Lecture 15

    • Cell signaling is crucial for cell survival.
    • Cells respond to external stimuli via cell signalling.
    • Signal molecules (ligands) can enter cells or bind to cell-surface receptors.
    • Receptors initiate intracellular actions when activated by ligands.
    • A cascade of protein conformational changes relays the signal within the cell.

    Cell Signaling Overview

    • Extracellular messenger molecules communicate between cells.
    • Autocrine signalling: cells signal themselves.
    • Paracrine signalling: adjacent cells communicate with short-distance messengers.
    • Endocrine signalling: messenger molecules (hormones) travel through the bloodstream to target cells.

    Signal Transduction

    • Extracellular messages (ligands) like steroids, neurotransmitters, and growth factors bind to receptors.
    • Conformational changes in the receptor relay the message to the cytoplasm.
    • Two major routes for message transmission:
      • Generation of a second messenger via an effector enzyme.
      • Recruitment of signaling proteins to initiate a cascade of protein activation.

    Signaling Pathways/Cascades

    • Each protein in a signaling pathway alters the shape of the next protein.
    • Protein conformation alterations often involve phosphorylation.
    • Kinases add phosphate groups.
    • Phosphatases remove phosphate groups.

    Protein Phosphorylation

    • Phosphorylation changes how proteins behave.
    • This can activate or inactivate enzymes and alter their function or location.
    • This includes effects on protein interactions, subcellular movement, and degradation.
    • Protein phosphorylation patterns differ between cell types.

    Circadian Control of Metabolism & Physiology

    • Phosphorylation plays a central role in circadian control of metabolism and physiology.

    Receptors

    • Receptors are proteins on target cells that receive messages.
    • Types of cell receptors include:
      • G-protein coupled receptors (GPCRs)
      • Receptor protein-tyrosine kinases (RTKs)
      • Ligand-gated channels
      • Steroid hormone receptors
      • Specialized receptors (e.g., B and T-cell receptors)

    G Protein-Coupled Receptors (GPCRs)

    • They are seven transmembrane helical domain receptors.
    • They are the largest family of membrane proteins.
    • They are coupled to cytoplasmic G proteins with three subunits (α, β, γ).
    • These receptors use GTP to activate their effector protein and trigger second messengers.
    • Ligands like amino acids, gases, steroids, eicosanoids, peptides, and proteins bind to the receptors.

    GPCR Signal Transduction

      1. Ligand binding alters the receptor's shape, increasing its affinity for G proteins.
      1. GDP on Ga is exchanged for GTP, activating the G protein.
      1. GTP-α dissociates from Gβγ and activates an effector protein, and Ga subunits lose their affinity for Gβγ.
      1. GTP-α can either activate or inhibit effector proteins (e.g., adenylate cyclase).

    GPCR Desensitization

    • Receptors can be desensitized through phosphorylation by G protein-coupled receptor kinase (GRK).
    • Arrestin binds to the phosphorylated receptor, inhibiting G protein binding and promoting receptor internalization.

    G Protein-Coupled Receptor Effectors

    • Different intracellular second messengers are triggered by different effectors, including cAMP, cyclic GMP, IP3, and DAG.
    • Hormones can trigger intracellular cascade of events to regulate cells’ response and behaviours.

    Human Diseases Linked to GPCR Pathway

    • Some diseases like Albright's hereditary osteodystrophy, pseudohypoparathyroidism, and McCune-Albright syndrome have defects in G proteins that regulate cell activity.
    • These defects can lead to abnormal bone development, precocious puberty, and hyperpigmentation.

    Next Lecture/Content

    • The next lecture will cover signal transduction (IP3, DAG, and PKC).

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    Description

    This quiz covers key concepts from Lecture 15 on the molecular mechanisms of disease, focusing on cell signaling processes. Topics include types of signaling such as autocrine, paracrine, and endocrine, as well as the mechanisms of signal transduction through receptor activation. Test your understanding of these fundamental cellular communication pathways.

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