Intracellular Signalling at the Cell Membrane

Question 1

the intracellular events that transform the extracellular signal into an intracellular signal

Answer 1

transduction

Question 2

examples of effectors

Answer 2

protein kinases or transcription factors

Question 3

An extracellular signal activates a ________

Answer 3

membrane-bound receptor

Question 4

receptor activation leads to an _______ cytosolic or membrane concentration of 2nd messenger

Answer 4

increased

Question 5

Single activated receptor → many molecules of 2nd messenger =

Answer 5

amplification

Question 6

signal termination is due to a number of processes (3)

Answer 6

1. inactivation of receptor (no 1st messenger) or receptor-associated effectors
2. degradation or removal of 2nd messenger
3. negative feedback

Question 7

name 3 types of cell membrane receptors

Answer 7

1. ion channel-coupled receptors
2. G-protein coupled receptors
3. enzyme-coupled receptors

Question 8

the largest family of cell membrane receptors are

Answer 8

G-protein-coupled receptors (GPCRs)

Question 9

800 unique G-protein-coupled receptors (GPCRs). Almost half of ________ act on these receptors or their pathways

Answer 9

medications

Question 10

GPCR: Receptor activation → activation of a protein that binds to a _____ nucleotide

Answer 10

guanine

Question 11

The activated G-protein is on a “timer”. Has intrinsic GTP-ase activity. When GTP hydrolyzed → GDP then the G-protein is
______

Answer 11

inactive

Question 12

Receptor = integral transmembrane protein. Spans the membrane _ times

Answer 12

7

Question 13

3 protein subunits:

Answer 13

α, β, γ

Question 14

α is bound to GDP, and βγ is bound to α

Answer 14

unstimulated

Question 15

α subunit releases GDP, replacing it with GTP and the α subunit disengages from the βγ subunits

Answer 15

Stimulated

Question 16

When the α unit hydrolyzes
GTP → GDP, it becomes
______ again

Answer 16

inactivated

Question 17

1. Ligand binds to receptor associated with a ___ G-protein
2. G_ releases GDP and binds GTP at the alpha subunit - by detaches from G-protein
3. G_ binds to and activates adenylyl cyclase
   - membrane-bound enzyme that converts ATP to cAMP
4. cAMP binds to protein kinase (PK A)
   - binds to inhibitors of PK A, which then detach, and allow the activate parts of PK A to work
5. PK A phosphorylates a multitude of effector proteins

Answer 17

Gs GPCR

Question 18

what enzyme converts ATP to cAMP

Answer 18

adenylyl cyclase

Question 19

what enzyme causes an inactivation of cAMP by converting it to 5’-AMP

Answer 19

cyclic AMP phosphodiesterase
- called the “turning off” process

Question 20

Stimulates adenylyl cyclase → cAMP production. cAMP activates PK A → phosphorylation of effectors

Answer 20

Gs

Question 21

biological impact of: Glycogenolysis,
thyroid hormone
synthesis

Answer 21

Gs

Question 22

alpha subunit Inhibits adenylyl
cyclase → decreased cAMP production. Decreases PK A activation.

Answer 22

Gi

Question 23

what pathway inhibits Gs pathways

Answer 23

Gi alpha

Question 24

beta-gamma Activates K+ channels*. Creates More negative cell membrane potential.

Answer 24

Gi

Question 25

Biological impact of reduction of heart rate

Answer 25

Gi beta-gamma

Question 26

Activates phospholipase C → IP3 and DAG production. IP3 → calcium release from ER. DAG → activation of BK C

Answer 26

Gq (a)

Question 27

Activates cGMP phosphodiesterase → decreased cGMP. Decreased cGMP → closes Na+ channels → more negative cell membrane potential.

Answer 27

Gt (a)

Question 28

biological impact: Detection of light – rod photoreceptors in retina

Answer 28

Gt (a)

Question 29

IP3 is a 2nd messenger that has one effect →

Answer 29

it causes release of Ca+2 from where it’s stored in the endoplasmic reticulum (ER)

Question 30

Ca+2 has many effects – it can bind to and activate a number of proteins

Answer 30

modulation of a very large range of effectors

Question 31

Good example of a Ca+2–binding protein:

Answer 31

calmodulin

Question 32

A “resting” cell (no calcium signal) has ___ micromolar of Ca+2 in the cytosol, and ____ mmol of calcium in the endoplasmic reticulum and in the extracellular space

Answer 32

0.1 micromolar and 1-3 mmol

Question 33

The concentration gradient for calcium for is very high → it ____ to enter the cytosol

Answer 33

“wants”

Question 34

A cell that is “activated” can reach Ca+2 concentrations of __ micromolar or more

Answer 34

10 mm

Question 35

When the concentration of Ca+2 ___ in the cytosol, then it will bind to calcium-binding proteins in the cytosol → an effect

Answer 35

increases

Question 36

Each calmodulin binds to ____ Ca+2 ions before it becomes activated

Answer 36

four

Question 37

IP3 is water soluble – it enters the

Answer 37

cytosol

Question 38

DAG is lipid soluble – it stays within the ________ and diffuses throughout it

Answer 38

cell membrane

Question 39

This is a ubiquitous inhibitory G-protein that downregulates the activity of Gs

Answer 39

Gi

Question 40

Opening of K+ channels brings the cell closer to its Nernst potential for K+. What is the nernst potential of K+

Answer 40

-90mV

Question 41

what does a very negative membrane potential cause?

Answer 41

it tends to cause most cells to be “less” activated

Question 42

What would be the impact on the membrane potential if sodium enters the cell?

Answer 42

Makes the membrane potential more positive

Question 43

If the channel allows sodium to enter → the membrane becomes more “inside-positive. This is known as ___________

Answer 43

depolarization

Question 44

If the channel allows more potassium to leave → the membrane becomes more “inside-negative”. This is known as __________

Answer 44

hyperpolarization

Question 45

T or F: Making the membrane more inside-positive or more inside-negative impacts the activation of certain membrane-associated proteins

Answer 45

True

Question 46

Making the membrane more inside-positive or more inside negative impacts the activation of certain membrane-associated proteins

Answer 46

intrinsic kinase activity

Question 47

The binding of ligand ________ the receptor and activates a tyrosine kinase within the receptor

Answer 47

dimerizes

Question 48

Ligand examples of RTKsgand examples

Answer 48

▪ Insulin ▪ Growth factors ▪ Cytokines

Question 49

what is a pathway that does not produce 2nd messengers?

Answer 49

RAS-RAF-MAP

Question 50

which system is our KEY insulin signalling system

Answer 50

PI-3-Kinase (PI3K) > Akt System

Question 51

nitric oxide synthase (NOs) on L-arginine

Answer 51

creates Nitric Oxide - a small molecule that rapidly degrades as it is a free radical

Question 52

what causes the activation of nitric oxide synthase (NOs)

Answer 52

an increase of cytosolic calcium

Question 53

Na in the cell is

Answer 53

low

Question 54

potassium in the cell is

Answer 54

high

Question 55

calcium in the cell is

Answer 55

low

Question 56

Transmembrane proteins with ligand-binding domain on the outer surface of the plasma membrane are called:

Answer 56

enzyme-coupled receptors

Question 57

Binding of ligand ______ the receptor and activates a tyrosine kinase within the receptor

Answer 57

dimerizes

Question 58

ligand examples of RTK

Answer 58

- insulin - growth factors - cytokines

Question 59

what is Ras-Raf-MAP kinase key for:

Answer 59

growth factors

Question 60

_____ is a key mediator that relaxes smooth muscle in a wide variety of blood vessels and visceral organs

Answer 60

Nitric oxide

Question 61

Very small, hydrophobic gas that _____ and quickly through cell membranes

Answer 61

diffuses easily

Question 62

▪ It’s a second messenger – one of the only ones that can diffuse across the cell membrane and impact other cells

Answer 62

Nitric Oxide