CELL BIOL (Perrino): Receptors

Question 1

What membrane proteins represent 50 percent of drug targets?

Answer 1

GPCR!!!

Question 2

Can a ligand bind to more than one GPCR, and can the receptor bind to more than one ligand?

Answer 2

YEAH! they can both bind to a lot of GPCRs and ligands, respectively

Question 3

How many transmembrane domains does EVERY GPCR have?

Answer 3

Seven! These domains are also the most conserved parts

Question 4

What parts of GPCRs are diverse?

Answer 4

The binding site AND the cytosolic domain

Question 5

Examples of ligands with a ton of receptors!

Answer 5

Adrenaline has 9. ACh has 5. serotonin has 15 GPCRs

Question 6

What cells, tissues, and organ systems express GPCR and enzyme linked receptors?

Answer 6

ALL OF ‘EM

Question 7

ALL alpha units of G protein serve to what?

Answer 7

serve as a GTPase to bind to GTP and then hydrolyze it

Question 8

Once ligand binds to GPCR, what’s the first step?

Answer 8

the G protein complex (alpha, beta, gamma) docks to receptor protein. receptor protein!

Question 9

What happens immediately after GDP-coupled alpha subunit binds to receptor?

Answer 9

GDP gets exchanged for GTP; and the BOTH alpha subunit and BY complex are considered activated

Question 10

What does GTP cause the ABY complex in g proteins to do?

Answer 10

it activates AND dissociates them!

well, A apart from BY

Question 11

Where do activated subunits go (usually the alpha)?

Answer 11

they find the TARGET protein on the cytosolic side of the membrane to attach to

Question 12

What does the hydrolysis of GTP coupled alpha subunit do?

Answer 12

It causes the alpha to dissociate from target protein. and then alpha reassembles with BY. LAST STEP IN GPCR

Question 13

describe cholera mechanism

Answer 13

binds to the α subunit so that it can no longer hydrolyze its bound GTP, causing it to remain in an active state that stimulates adenylyl cyclase indefinitely.

Question 14

In alpha-andrenergic receptor what does activated g protein alpha subunit do?

Answer 14

It inhibits adenylyl cyclase! no cAMP

Question 15

In alpha-andregenic receptor what does the activated BY complex do?

Answer 15

It activates the K+ channel for efflux of potassium

Question 16

In alpha-andregenic receptor, what does the hydrolysis of the GTP coupled alpha subunit do?

Answer 16

like always, it causes ABY to reassociate!

Question 17

What does pertussin toxin block?

Answer 17

the affects the GDP-ABY complex such that the subunits do not get activated because they remain bound. remember that it’s a Gi alpha for a target protein. So if it did work, the BY would probably be putting in work, just like the other alpha andregenic receptor examples.

Question 18

What does PKA mean?

Answer 18

Protein KinASE

Question 19

What does inactive PKA look like?

Answer 19

It has a dimeric regulatory subunit connected to an inactive catalytic dimeric subunit

Question 20

What does cAMP do to the inactive PKA?

Answer 20

It binds to the REGULATORY subunit to make a cAMP-regulatory subunit complex. Additionally, this causes the release of the catalytic subunits (both separate) and now they become ACTIVE!

Question 21

PKA activates what and blocks what in fight or flight?

Answer 21

active PKA inactivates glycogen synthesis and upregulates glycolysis production

Question 22

Why does ligand for somatostatin up regulation produce a longer PKA response than, say, flight or fight?

Answer 22

Ligand activates PKA like usualy, but the activated PKA phosphorylates CREB,which is a DNA bnidning protein that somatostatin hormone gene transcription

Question 23

is the cAMP/PKA cascade common in hormones?

Answer 23

Yup!

Question 24

How can you deactivate cAMP pathway?

Answer 24

1. PDE

2. phosphotase

Question 25

What does PDE stand for and what does it do?

Answer 25

Phosphodiesterase breaks phosphodiester bonds and converts cAMP to regular inactive AMP

Question 26

What does phosphotase do?

Answer 26

It removes phosphate groups from proteins, such as the CREB binding protein in the somastatin pathway

Question 27

How specific are regulatory protein phosphotases?

Answer 27

They're not specific at all. They're very promiscuous

Question 28

Main FX of phosphotases?

Answer 28

To dephosphorylate phosphate kinase dependent proteins

Question 29

First step in PKC cascade after ABY activation

Answer 29

phosphoLIPASE C gets actiated and then breaks up DAG-IP3

Question 30

Where does the free IP3 go?

Answer 30

it binds to a transporter on the lumen of the ER which causes a conformational change and therefore the release of CA++!!

Question 31

What does the release of Ca++ in the PKC cascade do?

Answer 31

the Ca++ binds to the PKA C (DAG also binds to the PKA C), and then it activates it.

Question 32

What does an acttvated PKA C do?

Answer 32

it phosphorylates a bunch of other proteins!

Question 33

is calcium way higher in the cell or outside the cell?

Answer 33

Outside has [CA++] concentration by ten thousand fold

Question 34

Why is Ca++ so low in the cytosol? (3 reason)

Answer 34

1. active transport to ER 2. active transport to MT 3. calcium binding molecules in cytosol

Question 35

What are the 2 ways to raise Ca++ in the cell?

Answer 35

1. voltage gated calcium channels in nerve cells! | 2. GPCR response that releases IP3 to bind to transporter on ER and allow CA++ to flow into cytosol

Question 36

In cardiac myocytes, instead of IP3 what activates calcium efflux outside of ER?

Answer 36

Addition of calcium coming from the plasma membrane

Question 37

Main mechanims for GPCR response? Occurs about 90 percent of time

Answer 37

the cAMP pathway that activates a PKA for fruther singaling

Question 38

Now, how common is the PKA C pathway?

Answer 38

pretty common but not nearly as common as the cAMP pathway

Question 39

In olfaction, what is the name of the target protein that activated Galpha

Answer 39

Adenylyl cyclase

Question 40

What does adenylyl cylcase do in olfaction?

Answer 40

it actiates cAMP cascade

Question 41

What does cAMP do in olfaction?

Answer 41

It binds to the Na+ transporter to allow sodium in and depolarize the cell. then signal goes to brain

Question 42

Describe the signalling pathway of rod cells in dark.

Answer 42

rhodopsin inactivated; Gt (transducin) inactivated; low PDE; cGMP is active ; cell is depolarized; and then high rate of synapse

Question 43

Describe signalling pathway of rod cells in light

Answer 43

Light activates rhodopsin and then G protein transducin is activated; this then activates phosphodiesterase PDE which then lowers the amount of cGMP (by breaking phosphodiesterbonds); and then therefore sodium channels close so the cell is hyperpolarized. low synapse rate

Question 44

What happens if a GCPR has been on far too long"

Answer 44

It gets desensitized

Question 45

What's the first step in the GPCR phophorylation process?

Answer 45

Activated GPCR stimulates GRK, GRRRRRRKK, to phophorylate the GPCR at MULTIPLE sites. so then

Question 46

What happens to the GPCR domain site after it's multiphosphorylated?

Answer 46

ARRESTIN bdinds onto the domain part of the GPCR, completely blocking the cytosolic domain

Question 47

How many domains do ALL tyrosine kinase receptors have?

Answer 47

JUST ONE!!!!!!!!!!!!! Unlike 7 in GPCR

Question 48

_____ are usually growth factors

Answer 48

receptor tyrosine kinases

Question 49

After receptor binds to RTK, what happens? And then what happens after that?

Answer 49

RTKs dimerize, and then they autophosphorylate each other

Question 50

Tyr phophoyrylation WITHIN kinase somain increases or decreases kinase activity? What about Tyr phosphorylation outside the domain?

Answer 50

INCREASES kinase activty? provides docking sites for binding of other signaling proteins