MODULE 7: Chapter 8.2

Question 1

What are G protein–coupled receptors (GPCRs)?

Answer 1

A large number of receptors involved in sensory perceptions such as vision, taste, and smell

GPCRs have an evolutionarily conserved structure with seven transmembrane α helices.

Question 2

What is the structural orientation of GPCRs?

Answer 2

The amino terminus is oriented towards the extracellular space, and the carboxyl terminus is exposed to the cytosol.

Question 3

What is the significance of the term ‘serpentine receptors’?

Answer 3

It refers to GPCRs due to their snake-like structure formed by seven transmembrane α helices.

Question 4

What role does the N-terminal domain of GPCRs play?

Answer 4

It often contains one or more carbohydrate functional groups.

Question 5

What is the function of adenylate cyclase (AC) in GPCR signaling?

Answer 5

Produces cAMP.

Question 6

What does the β2-adrenergic receptor (β2-AR) bind to?

Answer 6

Binds epinephrine.

Question 7

What is the role of β-adrenergic receptor kinase (βARK)?

Answer 7

Acts on β-adrenergic receptors as a specific G protein–coupled receptor kinase.

Question 8

What is the function of phosphodiesterase (PDE)?

Answer 8

Breaks down cAMP or cGMP.

Question 9

What does Gα represent in GPCR signaling?

Answer 9

A G protein subunit.

Question 10

What is the role of GTPase activating protein (GAP)?

Answer 10

Stimulates GTPase activity of G proteins to inhibit signaling.

Question 11

What is the function of guanine nucleotide exchange factor (GEF)?

Answer 11

Promotes GDP–GTP exchange to activate signaling.

Question 12

What is the significance of rhodopsin in GPCRs?

Answer 12

It was the first GPCR analyzed at the molecular level and contains a bound retinal molecule that absorbs light.

Question 13

What causes conformational changes in GPCRs?

Answer 13

Ligand binding on the extracellular side of the receptor.

Question 14

What are the three steps in G protein–coupled receptor signaling?

Answer 14

• Ligand-induced conformational changes in the GPCR and binding of the inactive heterotrimeric G protein
• Receptor-mediated stimulation of guanine nucleotide exchange in the Gα subunit
• Regulation of downstream effector processes by Gα–GTP and Gβγ complexes.

Question 15

What does the Gα subunit do in the inactive state?

Answer 15

Contains GDP bound and associates with the GPCR after receptor activation.

Question 16

How many different Gαβγ complexes can theoretically form in humans?

Answer 16

Approximately 1000 different complexes.

Question 17

What second messenger does Gsα stimulate?

Answer 17

cAMP.

Question 18

What is the role of Gqα?

Answer 18

Activates phospholipase C to generate DAG and IP3.

Question 19

What do GPCRs regulate in sensory perception?

Answer 19

Intracellular levels of second messengers.

Question 20

What hormones regulate glycogen degradation in liver cells?

Answer 20

• Glucagon
• Epinephrine.

Question 21

What type of signaling pathways do glucagon and epinephrine activate?

Answer 21

Shared and parallel downstream signaling pathways.

Question 22

How does glucagon signal in liver cells?

Answer 22

Binds to glucagon receptors and activates Gsα signaling to produce cAMP.

Question 23

What receptors does epinephrine bind to in liver cells?

Answer 23

• β2-adrenergic receptors
• α1-adrenergic receptors.

Question 24

What is the physiological role of glucagon?

Answer 24

Released in response to low blood glucose levels.

Question 25

What class of first messengers does epinephrine belong to?

Answer 25

Catecholamines.

Question 26

What type of proteins do glucagon and epinephrine activate in liver cells?

Answer 26

Gα proteins (Gsα or Gqα) ## Footnote This activation leads to parallel signaling pathways.

Question 27

What is glucagon?

Answer 27

A peptide hormone released by the pancreas in response to low blood glucose levels.

Question 28

Where are glucagon receptors primarily expressed?

Answer 28

Liver and adipocyte cells.

Question 29

Why is epinephrine sometimes called the 'fight or flight' hormone?

Answer 29

It is released from the adrenal medulla under times of acute stress.

Question 30

What are the physiological effects of epinephrine?

Answer 30

Increased heart rate and mobilization of energy stores through glycogen breakdown and lipolysis.

Question 31

What types of adrenergic receptors do catecholamines bind to?

Answer 31

α-adrenergic and β-adrenergic receptors.

Question 32

What is the function of adrenergic receptor agonists?

Answer 32

Activate receptor signaling by mimicking natural ligands.

Question 33

What do adrenergic receptor antagonists do?

Answer 33

Bind to receptors with high affinity and block the binding of physiological agonists.

Question 34

What is clonidine used for?

Answer 34

Treatment of high blood pressure and insomnia.

Question 35

What is the role of isoproterenol?

Answer 35

A potent β2 agonist used by asthmatics to relax smooth muscle in the lungs.

Question 36

Name an example of a β1-adrenergic receptor antagonist.

Answer 36

Metoprolol.

Question 37

What is the primary role of Gsα in signal transduction?

Answer 37

Facilitates binding to adenylate cyclase.

Question 38

What conformational change occurs in Gsα upon GTP binding?

Answer 38

Switch II helix region changes to interact with adenylate cyclase.

Question 39

What does PKA stand for?

Answer 39

Protein kinase A.

Question 40

What is the structure of inactive PKA?

Answer 40

R2C2 tetramer consisting of two regulatory subunits and two catalytic subunits.

Question 41

What triggers the activation of PKA?

Answer 41

Binding of cAMP to the regulatory subunits.

Question 42

What is a pseudosubstrate sequence?

Answer 42

A sequence in the regulatory subunit that mimics the substrate sequence recognized by the catalytic domain.

Question 43

What does the binding of cAMP to the regulatory subunits cause?

Answer 43

Dissociation of the regulatory and catalytic subunits.

Question 44

What are the three distinct metabolic responses activated by PKA in liver cells?

Answer 44

* Phosphorylation and inhibition of glycogen synthase * Phosphorylation and activation of enzymes for glycogen degradation * Phosphorylation and activation of enzymes for gluconeogenesis.

Question 45

What is the effect of cAMP phosphodiesterase?

Answer 45

Hydrolyzes cAMP to AMP, modulating its steady-state levels.

Question 46

What second messengers are generated by the hydrolysis of PIP2?

Answer 46

* DAG * IP3.

Question 47

What does DAG activate?

Answer 47

Protein kinase C (PKC).

Question 48

What does IP3 stimulate?

Answer 48

Ca2⁺ release from the endoplasmic reticulum.

Question 49

What is the G protein cycle?

Answer 49

Sequential stimulation of G protein signaling by GEF activity followed by activation of GTPase activity by GAPs.

Question 50

What is the role of GEF proteins?

Answer 50

Promote GDP–GTP exchange and activate signaling.

Question 51

What do GAPs do?

Answer 51

Stimulate the intrinsic GTP hydrolyzing activity of G proteins.

Question 52

What is the function of RGS proteins?

Answer 52

Regulate G protein signaling by stimulating GTPase activity.

Question 53

What is the role of G protein–coupled receptor kinases (GRKs)?

Answer 53

Phosphorylate GPCRs to mark them for recycling.

Question 54

What is βARK?

Answer 54

A specific type of GRK associated with β2-adrenergic receptors.

Question 55

What does β-arrestin do?

Answer 55

Binds to phosphorylated receptors and prevents reassociation with Gαβγ complex.

Question 56

How does receptor desensitization occur?

Answer 56

Through phosphorylation of the GPCR cytoplasmic domain, marking it for recycling.

Question 57

What is the role of coupled receptor kinase in GPCR signaling?

Answer 57

Provides a docking site for β-arrestin, preventing reassociation with Gαβγ complex.

Question 58

How is GPCR signaling terminated?

Answer 58

By recycling receptors through endocytic vesicles after ligand activation.

Question 59

What proteins phosphorylate the GPCR cytoplasmic tail?

Answer 59

G protein–coupled receptor kinase proteins, such as βARK.

Question 60

What does β-arrestin do in the context of GPCR signaling?

Answer 60

Binds to the phosphorylated receptor and facilitates its transport to endosomal compartments.

Question 61

What happens to GPCR after dephosphorylation in endocytic vesicles?

Answer 61

It is either degraded or returned to the plasma membrane.

Question 62

What is feedback inhibition in GPCR signaling?

Answer 62

Phosphorylation of GPCRs by downstream kinases like PKA, which affects receptor activity.

Question 63

What are the two domains of β-arrestin responsible for?

Answer 63

Recognizing phosphoserine and phosphothreonine residues on target proteins.

Question 64

What class of responses do most human GPCR genes account for?

Answer 64

Sensory perception (vision, smell, taste).

Question 65

How many G protein genes are encoded in the human genome?

Answer 65

17 Gα, 5 Gβ, and 12 Gγ genes.

Question 66

Why are fewer heterotrimeric G protein genes needed?

Answer 66

Selectivity of signal transduction depends on the receptor, not the signaling mechanism.

Question 67

What is rhodopsin?

Answer 67

A GPCR consisting of seven α helices and a bound retinal molecule that absorbs light.

Question 68

What is a heterotrimeric G protein?

Answer 68

A membrane-bound protein complex associated with GPCRs that dissociates upon receptor ligand binding.

Question 69

What is the function of GTPase?

Answer 69

Cleaves GTP to form GDP plus inorganic phosphate.

Question 70

What does glucagon signal?

Answer 70

Low glucose levels in the blood.

Question 71

What are catecholamines?

Answer 71

A class of first messenger hormones derived from tyrosine.

Question 72

What is a receptor agonist?

Answer 72

A compound that binds and activates a receptor protein.

Question 73

What is a receptor antagonist?

Answer 73

A compound that blocks receptor activation by preventing binding of the natural ligand.

Question 74

What is the role of protein kinase A (PKA)?

Answer 74

Activates numerous target proteins and enzymes in the cAMP signaling pathway.

Question 75

What is a guanine nucleotide exchange factor (GEF)?

Answer 75

A protein that promotes GDP–GTP exchange and activates signaling.

Question 76

What does the G protein cycle involve?

Answer 76

Sequential stimulation by GEF activity and activation of GTPase activity by GAPs.

Question 77

What is β-adrenergic receptor kinase (βARK)?

Answer 77

A kinase that phosphorylates the β2-adrenergic receptor to terminate its signal.

Question 78

What is the function of GTPase activating protein (GAP)?

Answer 78

Stimulates the intrinsic GTP hydrolyzing activity of G proteins.

Question 79

What is the role of G protein–coupled receptor kinase (GRK)?

Answer 79

Phosphorylates the GPCR cytoplasmic domain, marking it for recycling.