Signal Transduction IV

Question 1

Steroids, retinol, thyroid hormone, and vitamin D receptors are all what kinds of receptors?

Answer 1

Intracellular receptors

Question 2

What role do Intracellular receptors play in the cell?

Answer 2

They are ligand-dependent transcription factors. So they are present initially in the cytoplasm or the nucleus and when they become bound by ligands, they initiate transcription

Question 3

What kinds of signals use intracellular receptors?

Answer 3

small, hydrophobic

Question 4

mineralocorticoid receptors bind what ligand?

Answer 4

aldesterone

Question 5

androgen receptors bind what ligand?

Answer 5

testosterone

Question 6

T or F. All steroid receptors have DNA binding domains and variable N termini that are not vital to the function of the receptor

Answer 6

T.

Question 7

What terminal of steroid receptor is the ligand binding domain?

Answer 7

C terminus

Question 8

Do steroids bind to receptors on the cell surface or diffuse inside the cell?

Answer 8

they diffuse into the cell

Question 9

What are the steps of steroid hormone diffusion and binding inside a cell (for a cytoplasm receptor)?

Answer 9

1) hormone/ligand diffuses into the cell
2) hormone binds to a receptor in the cytoplasm and a conformational change (i.e. displaces the inhibitor heat shock protein) is induced and the receptor is ‘activated’
3) the activated receptor-hormone complex dimerizes and moves into the nucleus

4) once inside the nucleus the complex will interact with co-activators and RNA polymerase
and then sit down on a specific regulatory region of DNA (the HRE) upstream of a gene to influence transcription

Question 10

In order for a cell to be responsive to a steroid, what two things must it contain?

Answer 10

1) a receptor to bind the steroid

2) An HRE (hormone response element) on the DNA to bind the receptor/steroid complex

Question 11

Is HRE a specific response element? What for?

Answer 11

No. It is the term to describe all hormone response elements in the promoter region of genes

Question 12

Is GRE a specific response element? What for?

Answer 12

specific DNA sequence for glucocorticoid response element

Question 13

Is ERE a specific response element? What for?

Answer 13

specific DNA sequence for estrogen response element

Question 14

Inactive steroid receptors in the cytoplasm are often in complex with what?

Answer 14

inhibitory protein bound to the C-terminus. (usually a heat shock protein)

ligand binding will release the inhibitor

Question 15

HREs interact with what part of the receptor?

Answer 15

the DNA binding domain

Question 16

Steroid receptors can come from/start out which two places?

Answer 16

cytoplasm and nucleus

Question 17

What kinds of steroid receptors are found only in the nucleus and form heterodimers?

Answer 17

retinoic acid, vitamin D, and thyroid hormone

Question 18

What are the steps of steroid hormone diffusion and binding inside a cell for a nuclear receptor?

Answer 18

1) receptors exist naturally inside the nucleus dimerized with an RXR, another nuclear receptor (i.e. it is sitting on the DNA too), and bound to a co-repressor molecule. This entire complex is sitting down on the HRE region of the gene
2) ligand binding inside the nucleus causes dissociation of the co-repressor from the complex, RNA polymerase and co-activators are recruited and transcription can occur

Question 19

What kinds of steroid receptors are found only in the cytosol and form homodimers?

Answer 19

glucocorticoid, estrogen, and progesterone

Question 20

What effect do glucocorticoids have?

Answer 20

it primes gluconeogenesis

Question 21

How do glucocorticoids prime gluconeogenesis? (i.e. what does it induce expression of?)

Answer 21

It induces expression of PEP carboxykinase, fructose-1,6- biphosphate, and glu-6-p

it does this by up-regulating transcription of these things

Question 22

Is nitric oxide diffusable?

Answer 22

Yes.

Question 23

What is the major effect of NO?

Answer 23

it causes smooth muscle relaxation which increases blood flow

Question 24

What makes NO?

Answer 24

NOS (nitric oxide synthetase)

Question 25

What are the three forms of NOS?

Answer 25

ENOS- endothelial
INOS- inducible
NNOS- neuronal

Question 26

How is NO formed?

Answer 26

deamination of arginine by NOS (rxn also generates cytroline)

Question 27

What does NO do in the cell?

Answer 27

causes a soluble guanyl cyclase by binding to its heme group (which makes cGMP)

Question 28

How is cGMP (cyclic GMP) made?

Answer 28

by guanyl cyclase from GTP

Question 29

Describe cGMP induced metabolism

Answer 29

1) diffusible NO activates guanyl cyclase which produces cGMP from GTP.
2) cAMP activates PKG (protein kinase G) which then uses GTP to phosphorylate other proteins (aka a cascade vey similar to PKA cycle)

Question 30

Is production cGMP titly controlled?

Answer 30

yes

Question 31

what does cGMP phosphodiesterase do?

Answer 31

changes cGMP to 5’-GMP

Question 32

How does NO cause smooth muscle relaxation?

Answer 32

1) Ach released from a nerve terminal binds to NOS (thus activating it) on the endothelial, which then makes NO
2) NO rapidly diffuses into the smooth muscle cell and binds to target proteins, causing relaxation of muscle (and thus increased blood flow)

Question 33

What therapeutics work through the action of NO?

Answer 33

1) nitro-glycerin

2) viagra drug classes

Question 34

How does nitroglycerin work?

Answer 34

It breaks down in the bloodstream very slowly to release NO, which acts as a vasodilator to increase blood flow to the heart and relax the coronary arteries (for treatment of angina)

Question 35

How do viagra drugs work?

Answer 35

They block the action of cGMP phosphodiesterase, thus prolonging the effects of vasodilation caused by NO