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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?

It transmits the message into the cytoplasmic domain Signup and view all the answers

What is a characteristic of endocrine signaling?

It transmits signals through the bloodstream Signup and view all the answers

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

Second messengers Signup and view all the answers

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

Steroids and neurotransmitters Signup and view all the answers

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

Inhibits G protein binding and promotes internalization Signup and view all the answers

How does Gα subunit inactivate itself during signal transduction?

By slowly hydrolyzing GTP Signup and view all the answers

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

Activate calcium channels Signup and view all the answers

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

It phosphorylates various substrates Signup and view all the answers

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

Accelerate the rate of GTP hydrolysis Signup and view all the answers

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

Alters receptor conformation Signup and view all the answers

Which molecule is exchanged for GDP upon G protein activation?

GTP Signup and view all the answers

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

Dissociation from Gßγ subunits Signup and view all the answers

What second messenger is produced by adenylyl cyclase?

cAMP Signup and view all the answers

How does the Gα subunit return to its inactive state?

Through hydrolysis of GTP Signup and view all the answers

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

Decreases affinity for effectors Signup and view all the answers

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

Receptor phosphorylation Signup and view all the answers

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

It inhibits further G protein binding Signup and view all the answers

What happens to desensitized receptors after they are dephosphorylated?

They are returned to the cell membrane Signup and view all the answers

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

Hydrolyze membrane phospholipids Signup and view all the answers

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

Trigger second messengers in signal transduction Signup and view all the answers

Which of the following correctly describes the structure of GPCRs?

7 transmembrane helical domains Signup and view all the answers

What happens upon ligand binding to a GPCR?

Conformational change of the receptor Signup and view all the answers

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

Gα subunit dissociates and binds to effector Signup and view all the answers

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

Carbohydrates Signup and view all the answers

What is the role of GTP in G protein signaling?

It activates the G protein Signup and view all the answers

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

Adenylyl cyclase Signup and view all the answers

What characterizes the heterotrimeric G protein?

It is composed of α, ß, and γ subunits Signup and view all the answers

How does Gα affect the activity of effector proteins?

It can activate or inhibit effector proteins Signup and view all the answers

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

GTP is converted into GDP and Pi Signup and view all the answers

What results from the conformational change of Gα?

Increased affinity for Gβγ subunits Signup and view all the answers

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

Arrestin Signup and view all the answers

Which process does Arrestin promote?

Internalization of GPCRs Signup and view all the answers

What occurs after Arrestin binds to the GPCR?

G protein binding is inhibited Signup and view all the answers

What happens to GPCRs after internalization?

They are dephosphorylated and returned to the membrane Signup and view all the answers

What does the hydrolysis of GTP by Gα indicate?

Termination of the G protein's action Signup and view all the answers

How does phosphorylation of the receptor affect G protein binding?

It reduces G protein binding Signup and view all the answers

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

To modulate effector proteins Signup and view all the answers

Which of the following is a result of protein phosphorylation?

Activation of metabolic enzymes Signup and view all the answers

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

It can alter the protein's subcellular location. Signup and view all the answers

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

Peptide hormone receptors Signup and view all the answers

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

They add phosphate groups to target proteins. Signup and view all the answers

How do different cell types exhibit variability in protein phosphorylation?

Due to differences in phospho patterns. Signup and view all the answers

Which amino acids are primarily involved in protein phosphorylation?

Serine, threonine, tyrosine Signup and view all the answers

Which statement best describes a function of signaling pathways?

They mediate responses leading to alterations in cell activities. Signup and view all the answers

What is the role of epinephrine in glucose regulation?

Activates adrenergic GPCR in the liver to stimulate glucose release Signup and view all the answers

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

Gs subunit Signup and view all the answers

What effect do beta blockers have on the cardiovascular system?

Decrease heart rate and force of contraction Signup and view all the answers

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

Activates cAMP production in liver cells Signup and view all the answers

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

Inhibits cAMP production Signup and view all the answers

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

Binding of a ligand to the receptor Signup and view all the answers

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

GTP-Gα subunit Signup and view all the answers

What is the role of phospholipase C in GPCR signaling?

Convert PIP2 into inositol trisphosphate and diacylglycerol Signup and view all the answers

What type of second messenger is generated by adenylyl cyclase?

cAMP Signup and view all the answers

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

Gα subunit Signup and view all the answers

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

Returns Gα to inactive state Signup and view all the answers

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

Glucose Signup and view all the answers

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

Three subunits Gα, Gβ, and Gγ Signup and view all the answers

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

Regulates other effectors Signup and view all the answers

What occurs after the Gα subunit hydrolyzes GTP to GDP?

It increases affinity for Gβγ subunits. Signup and view all the answers

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

It binds to the receptor and inhibits G protein binding. Signup and view all the answers

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

Phosphorylation of the receptor by GRK. Signup and view all the answers

What happens to GPCRs once they are internalized?

They can be dephosphorylated and recycled back to the membrane. Signup and view all the answers

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

It reduces the affinity for effector proteins while increasing affinity for Gβγ. Signup and view all the answers

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

It inactivates the Gα subunit and stops the signal. Signup and view all the answers

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

G Protein-Coupled Receptor Kinase (GRK) Signup and view all the answers

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

It inhibits G protein binding. Signup and view all the answers

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

It activates the Gα subunit. Signup and view all the answers

What occurs when arrestin binds to a GPCR?

It inhibits interaction with G proteins. Signup and view all the answers

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

It leads to the inactivation of the Gα subunit. Signup and view all the answers

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

Cyclic adenosine monophosphate (cAMP) Signup and view all the answers

What occurs to GPCRs after they undergo internalization?

They are recycled back to the cell membrane. Signup and view all the answers

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

They can activate glycogen synthesis pathways. Signup and view all the answers

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

They organize and stabilize PKA interactions at specific cellular locations. Signup and view all the answers

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

They accelerate the rate of GTP hydrolysis by Gα. Signup and view all the answers

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

Stimulated breakdown of glycogen and enhanced glucose regulation. Signup and view all the answers

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

It promotes internalization and desensitization of the receptor. Signup and view all the answers

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

Induction of cell proliferation and potential malignancies. Signup and view all the answers

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

Glucose Signup and view all the answers

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

Increased rate and force of contraction Signup and view all the answers

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

It activates Gi subunit to inhibit cAMP production Signup and view all the answers

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

Glucagon Signup and view all the answers

What mechanism do beta blockers utilize to lower blood pressure?

Blocking the effects of epinephrine Signup and view all the answers

What is a key difference between autocrine and paracrine signaling?

Autocrine signaling involves receptors on the same cell, while paracrine signaling involves nearby cells. Signup and view all the answers

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

It promotes glycogen breakdown. Signup and view all the answers

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

Signal transduction Signup and view all the answers

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

Lipids, proteins, and vitamins Signup and view all the answers

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

It generates second messengers. Signup and view all the answers

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

Conformational change of the receptor Signup and view all the answers

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

Endocrine signaling Signup and view all the answers

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

The receptor undergoes a conformational change. Signup and view all the answers

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

It converts GTP to GDP and Pi. Signup and view all the answers

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

Decreases affinity for effector proteins and increases affinity for Gβγ subunits. 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?

Gα dissociates from Gßγ and binds to an effector protein. Signup and view all the answers

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

It phosphorylates the receptor. Signup and view all the answers

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

It promotes receptor internalization. Signup and view all the answers

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

Gα reverts to its GDP-bound state, decreasing effector affinity. Signup and view all the answers

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

The receptor is internalized and tagged for degradation. Signup and view all the answers

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

It promotes receptor desensitization and internalization. Signup and view all the answers

What occurs to GPCRs after they are desensitized and dephosphorylated?

They are returned to the cell membrane and resensitized. Signup and view all the answers

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

It converts ATP to cAMP, serving as a second messenger. Signup and view all the answers

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

It decreases the effectiveness of signal transduction. Signup and view all the answers

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

They are marked for recycling back to the membrane. Signup and view all the answers

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

Gα decreases its affinity for both effector proteins and Gßγ subunits. Signup and view all the answers

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

Deactivation of Gα, thus stopping the signal. Signup and view all the answers

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

By hydrolyzing GTP into GDP and Pi. Signup and view all the answers

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

They can activate their own signaling pathways independently. Signup and view all the answers

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

Preparation of the receptor for degradation. Signup and view all the answers

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

Activates or inhibits effector proteins. Signup and view all the answers

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

It alters the receptor conformation, increasing G protein affinity. Signup and view all the answers

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

Cell proliferation and potential malignancies Signup and view all the answers

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

Binding of cAMP to regulatory subunits Signup and view all the answers

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

Amplification of the signal response Signup and view all the answers

Which process is triggered by the activation of adenylyl cyclase?

Increase in intracellular cAMP levels Signup and view all the answers

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

Produces inositol trisphosphate (IP3) and diacylglycerol (DAG) Signup and view all the answers

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

Hydrolysis rate of GTP by Gα subunit Signup and view all the answers

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

Formation of cyclic nucleotides Signup and view all the answers

What happens to GPCRs after they are internalized following desensitization?

They undergo dephosphorylation and can be resensitized Signup and view all the answers

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

Phosphorylated proteins Signup and view all the answers

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.