Cell Signaling 2

Question 1

What are some common stimuli for GPCRs?

Answer 1

Light
Smells
Taste
Ions
Amino Acids
Lipids
Etc

Question 2

What percent of pharmaceuticals target GPCRs

Answer 2

50%

Question 3

How many membrane bound proteins does a GPCR require?

Answer 3

3

Question 4

What are the 3 proteins required by a GPCR?

Answer 4

Receptor
G Protein
Amplifier

Question 5

What are the 3 basic domains of a GPCR?

Answer 5

Transmembrane
N Terminus
C Terminus

Question 6

How many transmembrane domains does a GPCR have?

Answer 6

7

Question 7

What is the function of the N Terminus domain of a GPCR?

Answer 7

Ligand binding

Question 8

What solution is the C Terminus in? ECM or Cytosol?

Answer 8

Cytosol

Question 9

Describe the structure of the G Protein

Answer 9

Heterotrimeric

Alpha, Beta, Gamma Subunits

Question 10

In the inactive state, what does the alpha subunit bind to?

Answer 10

GDP Molecule

Question 11

What happens at the Alpha subunit binding site when the GPCR is activated?

Answer 11

It releases the GDP in favor of GTP

GTP binding causes the alpha subunit to be released by the BETA/GAMMA complex

Question 12

How is the active Alpha subunit/GTP complex deactivated?

Answer 12

Hydrolysis of GTP via GTPase that is intrinsic to the alpha subunit

Question 13

What factor, represented by GEF helps catalyze the exchange between GDP and GTP during receptor activation?

Answer 13

Guanine Nucleotide Exchange Factor

Question 14

How is the alpha subunit attached to the membrane?

Answer 14

Lipid anchor

Question 15

What are the 3 primary Amplifier (effector) proteins that are known to interact with GTP bound Alpha subunits?

Answer 15

Adenyl cyclase (AC)
Phospolipase C (PLC)
RhoA

Question 16

What are the 4 groups of G proteins?

Answer 16

Galpha(s)
Galpha(i)
Galpha(q)
Galpha(12/13)

Question 17

Which G protein increases Adenyl cyclase?

Answer 17

G alpha (s)

Question 18

Which G protein increases PLC?

Answer 18

G alpha (q)

Question 19

What does G alpha (i) do?

Answer 19

Inhibits Adenyl cyclase

Question 20

What does G alpha (12/13) do?

Answer 20

Stimulates RhoA production

Question 21

So if the alpha subunits is interacting with the amplifier proteins, what 3 molecules does the B/G subunit target?

Answer 21

K+ Channels
Adenyl cyclase
Pholpholipase C

Question 22

If some signaling molecules can interact with GPCRs and Ionoreceptors how does the body keep things straight?

Answer 22

Because the response to the same signal molecules is tissue specific and receptor specific.

So acetylcholine will induce a different response if it is picked up by a ionoreceptor than a GPCR. It will also induce a different response in cardiac vs. smooth muscle.

Question 23

What is the name of the ligand-gated receptor that recognizes Acetylcholine?

Answer 23

Nicotinic

Question 24

What is the name of the GPCR that recognized Acetylcholine?

Answer 24

Muscarinic

Question 25

What G protein is activated in smooth muscle?

Answer 25

G (q) | Activates muscle contraction

Question 26

What G protein is activated in cardiac muscle by Acetylcholine?

Answer 26

G (i) | Inhibits muscle contraction

Question 27

Which G proteins interact with Alpha Receptors?

Answer 27

``` A1 = G (q) A2 = G (i) ```

Question 28

Which G proteins interact with Beta Receptors?

Answer 28

Just G (s)

Question 29

What are adrenergic receptors?

Answer 29

They interact with Adrenaline and Noradrenaline | Alpha/Beta Receptors

Question 30

If the hormone is the UPS guy that delivers a package to a home, what is a 2nd messenger?

Answer 30

It would be like the butler who answered the door, took the package in the house and then delivered it to the owner.

Question 31

What are the 5 primary 2nd Messengers?

Answer 31

``` Cyclic AMP (cAMP) Cyclic GMP (cGMP) IP3 DAG Ca2+ ```

Question 32

What molecule is cAMP derived from?

Answer 32

ATP

Question 33

Which G protein stimulates cAMP production?

Answer 33

G alpha (s)

Question 34

Which G protein inhibits cAMP production?

Answer 34

G alpha (i)

Question 35

What molecule does Phospholipase C hydrolyze?

Answer 35

PIP2

Question 36

When PIP2 is cut by PLC, what molecules are created?

Answer 36

DAG and IP3

Question 37

What GTP bound G protein activates the PLC/DAG pathway?

Answer 37

G alpha (q)

Question 38

What G protein subunit is stimulated by the Cholera Toxin?

Answer 38

G alpha (s)

Question 39

What are the 2 subtypes of PLC?

Answer 39

PLC Beta | PLC Gamma

Question 40

Which PLC subtype is used in the PIP2/DAG pathway?

Answer 40

PLC Beta

Question 41

Which G protein interacts with PLC-Beta

Answer 41

G alpha (q)

Question 42

When PIP2 is chopped, which molecule stays in the membrane?

Answer 42

The lipid soluble DAG

Question 43

If DAG stays in the membrane, what happens to IP3?

Answer 43

It diffuses to the ER/SR to release Ca2+ ions into the cytoplasm

Question 44

What molecule is cGMP derived from?

Answer 44

GTP

Question 45

What is a Guanylyl Cyclase Protein?

Answer 45

GCs can be associated with the membrane or in the cytosol. They act as receptors and transducer in the signaling pathway

Question 46

How many transmembrane domains does GC have?

Answer 46

1 The Extracellular portion is the receptor, the intracellular portion is the transducer

Question 47

What is the abbreviation of the membrane GC?

Answer 47

pGC | p (particulate)

Question 48

What is the abbreviation for the soluble GC?

Answer 48

sGC

Question 49

What is the activator ligand for pGC?

Answer 49

Natriuretic peptides

Question 50

What is the activator ligand for sGC?

Answer 50

Nitric oxide

Question 51

How is nitric oxide produced?

Answer 51

From Nitric Oxide Synthase (NOS)

Question 52

Where is NOS located?

Answer 52

Nerve terminals and Endothelial cells

Question 53

What is the difference between nNOS and eNOS

Answer 53

``` n = nerve e = endothelial ```

Question 54

So what is the end result of GC activation?

Answer 54

Stimulation of cGMP production.....cGMP is a 2nd Messenger