GPCR Signalling

Question 1

What are G protein-coupled receptors (GPCRs)?

Answer 1

The largest family of cell surface receptors, comprising over 800 in humans.

Question 2

What is the structure of GPCRs?

Answer 2

They have 7 transmembrane spans across the lipid bilayer.

Question 3

What are the three subunits of trimeric G proteins?

Answer 3

• α
• β
• γ

Question 4

How are G proteins activated?

Answer 4

When bound to GTP.

Question 5

What happens when G proteins hydrolyze GTP?

Answer 5

They become inactive by converting GTP to GDP.

Question 6

What is a second messenger?

Answer 6

A rapidly produced diffusible signalling molecule that activates effector proteins.

Question 7

What is the effect of GPCR-mediated activation of G proteins?

Answer 7

Targets include ion channels and membrane-bound enzymes.

Question 8

What role do second messengers play in signal transduction?

Answer 8

They amplify the signal rapidly and are inactivated quickly.

Question 9

What is the function of adenylyl cyclase?

Answer 9

Converts ATP into the second messenger cAMP.

Question 10

What are the second messengers produced by phospholipase C?

Answer 10

• DAG
• IP3 (cleaved from PIP2)

Question 11

What is the role of Protein Kinase C (PKC)?

Answer 11

Activated at the membrane and involved in various signaling pathways.

Question 12

What is the significance of Ca2+ in GPCR signaling?

Answer 12

Regulates effector proteins through calmodulin.

Question 13

What is the principle of signal transduction related to termination?

Answer 13

Signaling must be terminated; this involves receptor internalization and degradation.

Question 14

Fill in the blank: cAMP is rapidly inactivated by _______.

Answer 14

Phosphodiesterase

Question 15

True or False: Second messengers are not involved in amplifying the signal.

Answer 15

False

Question 16

What is the role of guanine exchange factors (GEF) in GPCR signaling?

Answer 16

They facilitate the activation of G proteins.

Question 17

What is the role of regulators of G protein signaling (RGS)?

Answer 17

They help in the inactivation of G proteins.

Question 18

What is the function of diacylglycerol (DAG)?

Answer 18

It acts as a second messenger involved in activating PKC.

Question 19

What is the relationship between ligand binding and cellular response?

Answer 19

The more ligand binding, the greater the cellular response.

Question 20

What type of kinase is Protein Kinase A (PKA)?

Answer 20

A serine-threonine protein kinase.

Question 21

What triggers the release of Ca2+ as a second messenger?

Answer 21

The activation of IP3.

Question 22

What are the main groups of phospholipases C?

Answer 22

• PLCγ
• PLCδ
• PLCβ

Question 23

What is the main lipid content of cellular membranes that phospholipases act upon?

Answer 23

Phosphatidylcholine and phosphatidylinositol.

Question 24

What is the result of increased Ca2+ levels in cells?

Answer 24

Altered target protein activity, including activation of CaMK.

Question 25

What is the function of inositol phospholipids in signaling?

Answer 25

They dynamically regulate signaling pathways in response to extracellular signals.

Question 26

What activates GPCRs?

Answer 26

Extracellular ligands E.g. Glucagon, adrenaline, dopamine, histamine

Question 27

What inactivates GPCRs?

Answer 27

Phosphorylation and internalisation Residues that can be phosphorylated are serine, tyrosine and threonine only

Question 28

What are trimeric G proteins?

Answer 28

In the inactive state, the G protein consists of a trimeric complex located in the plasma membrane In the active state, the trimeric G protein complex can dissociate —> alpha dissociates from beta/gamma complex

Question 29

What happens when G proteins interact with ion channels?

Answer 29

Causes an immediate change in cell behaviour

Question 30

What happens when G proteins interact with membrane bound enzymes?

Answer 30

Enzyme activation leads to the production of intracellular signalling molecules that act as second messengers

Question 31

PKA and gene transcription

Answer 31

1. Activation of PKA in the cytosol 2. Translocation to the nucleus 3. Phosphorylation of transcription factors 4. Increased or suppressed transcription of target genes

Question 32

Inositol phospholipids

Answer 32

Question 33

How is DAG and IP3 involved in Protein kinase C translocation?

Answer 33

- PKC is recruited to the membrane from the cytosol - DAG brings the PKC to the membrane - PKC is activated at the membrane but not fully - IP3 triggers release of Ca2+ from the endoplasmic reticulum - The released Ca2+ binds to PKC and fully activates it

Question 34

Structure of conventional PKC

Answer 34

Question 35

Other PKCs

Answer 35

Novel PKC, group B —> do not have a C2 = Ca-independent and PL sensitive Atypical PKC, group C —> do not have a C1 and are missing a part of C2 = Ca-independent and PL insensitive