Signal Transduction IV Flashcards
Steroids, retinol, thyroid hormone, and vitamin D receptors are all what kinds of receptors?
Intracellular receptors
What role do Intracellular receptors play in the cell?
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
What kinds of signals use intracellular receptors?
small, hydrophobic
mineralocorticoid receptors bind what ligand?
aldesterone
androgen receptors bind what ligand?
testosterone
T or F. All steroid receptors have DNA binding domains and variable N termini that are not vital to the function of the receptor
T.
What terminal of steroid receptor is the ligand binding domain?
C terminus
Do steroids bind to receptors on the cell surface or diffuse inside the cell?
they diffuse into the cell
What are the steps of steroid hormone diffusion and binding inside a cell (for a cytoplasm receptor)?
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
In order for a cell to be responsive to a steroid, what two things must it contain?
1) a receptor to bind the steroid
2) An HRE (hormone response element) on the DNA to bind the receptor/steroid complex
Is HRE a specific response element? What for?
No. It is the term to describe all hormone response elements in the promoter region of genes
Is GRE a specific response element? What for?
specific DNA sequence for glucocorticoid response element
Is ERE a specific response element? What for?
specific DNA sequence for estrogen response element
Inactive steroid receptors in the cytoplasm are often in complex with what?
inhibitory protein bound to the C-terminus. (usually a heat shock protein)
ligand binding will release the inhibitor
HREs interact with what part of the receptor?
the DNA binding domain
Steroid receptors can come from/start out which two places?
cytoplasm and nucleus
What kinds of steroid receptors are found only in the nucleus and form heterodimers?
retinoic acid, vitamin D, and thyroid hormone
What are the steps of steroid hormone diffusion and binding inside a cell for a nuclear receptor?
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
What kinds of steroid receptors are found only in the cytosol and form homodimers?
glucocorticoid, estrogen, and progesterone
What effect do glucocorticoids have?
it primes gluconeogenesis
How do glucocorticoids prime gluconeogenesis? (i.e. what does it induce expression of?)
It induces expression of PEP carboxykinase, fructose-1,6- biphosphate, and glu-6-p
it does this by up-regulating transcription of these things
Is nitric oxide diffusable?
Yes.
What is the major effect of NO?
it causes smooth muscle relaxation which increases blood flow
What makes NO?
NOS (nitric oxide synthetase)
What are the three forms of NOS?
ENOS- endothelial
INOS- inducible
NNOS- neuronal
How is NO formed?
deamination of arginine by NOS (rxn also generates cytroline)
What does NO do in the cell?
causes a soluble guanyl cyclase by binding to its heme group (which makes cGMP)
How is cGMP (cyclic GMP) made?
by guanyl cyclase from GTP
Describe cGMP induced metabolism
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)
Is production cGMP titly controlled?
yes
what does cGMP phosphodiesterase do?
changes cGMP to 5’-GMP
How does NO cause smooth muscle relaxation?
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)
What therapeutics work through the action of NO?
1) nitro-glycerin
2) viagra drug classes
How does nitroglycerin work?
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)
How do viagra drugs work?
They block the action of cGMP phosphodiesterase, thus prolonging the effects of vasodilation caused by NO
