3. Receptors and Cell Signaling

Question 1

Where are the receptors for hydrophilic signaling molecules invariably located?

Answer 1

On the exterior of the plasma membrane.

Question 2

What is the example given for Endocrine signaling?

Answer 2

Epinephrine (Short acting - despite what the slide says)

Question 3

What is the example given for Paracrine signaling?

Answer 3

Testosterone

Question 4

What is the example given for Autocrine signaling?

Answer 4

Interleukin-1

Question 5

What is the example given for Direct / Juxtacrine signaling?

Answer 5

Heparin-binding epidermal growth factor

Question 6

What are the seven steps of the trimeric G Protien signal relay?

Answer 6

1. Ligand binds
2. Conformational change
3. GPCR binds to G Protien
4. GPCR acts as a GEF (Guanidine Exchange Factor)
5. G_alpha trades its GDP for GTP
6. Activated G_alpha activates or inhibits effector molecule
7. The effector molecule catalyzes the reaction!

Question 7

What intrinsic portion of the G Protein hydrolyses GTP to GDP to turn itself off?

What subunit houses this activity?

Answer 7

intrinsic GTPase

alpha subunit

Question 8

Trimeric G Protiens will eventually release GTP and turn back off, but what enzyme makes this trade happen faster?

Answer 8

GTPase Activating protien

Question 9

What is the function of the G_s G protien?

What second messenger is released as a result?

What enzyme does this second messenger activate?

And what does THAT thing do?

Answer 9

Simulation of Adenylate Cyclase

cAMP

PKA

Phosphorylates a target protien.

Question 10

What is the function of the Gt G protien?

What does that protien do?

What type of signaling is this?

Answer 10

Stimulation of cGMP phosphodiesterase

Catalyzes the elimination of cGMP

Negative signaling (cGMP does something, but this mechanism stops it)

The T in Gt means “Turn off the light!”

Question 11

What is the function of the Gi G protien?

What is the result?

Answer 11

Inhibition of adenylate cyclase

cAMP is not produced, and PKA is not activated.

Question 12

1. What is the function of the Gq G protien?
2. What happens as a result? (2 things)
3. What enzyme is activated, and what second messenger is released?

Answer 12

1. Activates phospholipase C
2. PIP is turned into IP3 and DAG
3. IP₃ opens a Calcium channel
4. DAG and calcium activate PKC
5. Calcium + Calmodulin is released to influence other protiens.

Question 13

What signal molecules use Gs?

Answer 13

Epinephrine (using beta-adrenergic receptors)

Histamine

I get Scared (epinephrine) by Bees (beta adrenergic) ‘cause I’m allergic (histamine), so I’m Gonna Scream (Gs)

Question 14

What signal molecules use Gi?

Answer 14

Epinephrine (using an alpha-adrenergic receptor)

Dopamine

Say _no (_inhibitor) to dope (dopamine), even if it’s scary (epinephrine), then you’ll be the alpha

Question 15

What signal molecules use Gq?

Answer 15

Acetylcholine

Stylish men train their muscles

_(_GQ is a men’s style magazine, acetylcholine activates muscles)

Question 16

What signal uses Gt?

Answer 16

Light

• Turn off the light!*
• Gt triggers cGMP phosphodiesterase to turn the cGMP signal off.*

Question 17

How does caffeine affect the heart?

Answer 17

It inhibits cAMP PDE

cAMP increases heart rate, and cAMP PDE gets rid of cAMP. Since caffeine stops cAMP PDE from getting rid of cAMP, cAMP stays high, and heart rate does too.

Question 18

Why are ED meds contraindicated in patients taking nitrates?

Answer 18

NO (nitrates) increase cGMP production to increase vasodilation

ED meds inhibit the breakdown of cGMP, effectively raising the concentration as well.

The combination of the two cGMP increasing factors can result in deadly drops in blood pressure!

Question 19

For Cholera

What G protien and subunit is affected?

What is changed on this protein?

What is overproduced as a result?

What causes the symptoms?

Answer 19

G_s alpha subunit

It has decreased GTPase activity

Gs alpha is stuck on, stimulating Adenylate Cyclase to be stuck on as well.

cAMP is overproduced

Cl- channels are left open, causing electrolyte and water loss.

Question 20

For pertussis

What G protien and subunit is affected?

What happens to the G protien?

What happens as a result?

Answer 20

Gi alpha subunit

Ribosylation prevents alpha subunit dissociation (part of activation)

Since Gi is in charge of stopping adenylate cyclase, AC is left on and too much cAMP is produced. Fluid and mucous floods the airway.

Question 21

What do G protein receptor kinases (GRKs) do?

How do they do it? (and what other protien helps?)

Where does this happen?

Answer 21

The inactivate G Protein coupled receptors (GPCRs)

They phosphorylate the GPCR, then an arrestin protien binds and prevents conformational change so that GDP cannot become GTP

The 3rd intracellular loop (cytosolic side)

Question 22

For Receptor Tyrosine Kinases (RTK’s)

What happens after the signal binds? (2)

Where do the intracellular adapter / docking protiens bind?

Answer 22

The receptor dimerizes and autophosphorylates

To the phosphorylated Tyrosine residues

Question 23

After a Receptor Tyrosine Kinase becomes phosphorylated and recruits its adapter and docking protiens, what two pathways can it use to trigger the protien targets?

Which one uses MAPK?

What is MAPK?

Answer 23

RAS-dependent - uses MAPK

RAS independent

A monomeric G Protein

Question 24

What is the clinical relevance of RAS or its separate GEFs?

Answer 24

They have been implicated in a wide range of cancers.