01a: Hormone-Receptor Interactions

Question 1

T/F: All hormones, to initiate a response, must bind to receptors on target cells.

Answer 1

False - receptors can be inside target cell

Question 2

T/F: Hormone-Receptor Interaction has both high specificity and high affinity.

Answer 2

True

Question 3

T/F: Hormone-Receptor interaction, in many cases, is a simple, unimolecular, reversible reaction.

Answer 3

False - simple, bimolecular, reversible

Question 4

In order for H-R complexes to form in presence of low hormone levels, (KA/KD) constant must be very high, which means (KA/KD) is very (high/low).

Answer 4

KA;
KD (reciprocal of KA)
Low

Question 5

T/F: Frequently, the H-R interaction is defined by its KA.

Answer 5

False - by its KD

Question 6

If the free hormone concentration is equal to KD, what does that tell you about the receptors?

Answer 6

Half are occupied/bound

Question 7

In order to have about 90% occupancy of hormone receptors, (X) should be increased (Y)-fold over (Z).

Answer 7

X = free hormone concentration
Y = 10
Z = KD

Question 8

If there’s about 10% occupancy of hormone receptors, (X) must be (Y)-fold greater than (Z).

Answer 8

X = KD
Y = 10
Z = free hormone concentration

(or free hormone concentration is 1/10 of KD)

Question 9

T/F: Nearly the full range of receptor occupancy can be obtained by varying free hormone concentration by one order of magnitude above/below KD.

Answer 9

True

Question 10

T/F: Upon release of a hormone, the hormone-receptor interaction occurs in all tissues.

Answer 10

False - only responsive tissues (sensitive to that hormone)

Question 11

Hormones that are derivatives of (X) are too polar to pass through (Y) and too large to pass through (Z).

Answer 11

X = peptides and amines
Y = lipoprotein membranes (diffusion)
Z = membrane pores

Question 12

List the two general groups of (membrane/cytoplasmic) receptors for water-soluble hormones.

Answer 12

Membrane;

1. Serpentine (7 membrane-spanning domains)
2. Single membrane-spanning domains

Question 13

G-proteins are hetero-(dimers/trimers/tetramers). Alpha-subunit is a(n) (X) and is predominantly bound to (Y).

Answer 13

Hetero-trimer;
X = GTPase
Y = GDP, beta-gamma subunit, and receptor

Question 14

Gs(alpha) is a (stimulatory/inhibitory) protein for (X), which (activates/forms/inhibits) (Y), which (activates/inhibits/forms) (Z).

Answer 14

Stimulatory;
X = AC
Forms;
Y = cAMP (from ATP)
Activates;
Z = PKA

Question 15

Describe the exact mechanism by which cAMP activates PKA.

Answer 15

Binds regulatory subunits and causes dissociation of active, catalytic subunits from the complex

Question 16

T/F: PKA has multiple substrates, all of which are in the cytoplasm.

Answer 16

False - can also affect transcription of target genes in nucleus

Question 17

Gq(alpha) (activates/inhibits) (X), which target/action?

Answer 17

Activates;
X = PLC

Cleaves PIP2 (into IP3 and DAG)

Question 18

IP3 is formed by (X) with which function?

Answer 18

X = cleavage of PIP2

Mobilizes Ca from vesicular storage

Question 19

DAG is formed by (X) with which function?

Answer 19

X = cleavage of PIP2

Activates PKC in the presence of Ca

Question 20

PIP2 can either be cleaved by (X) or acted on by (Y). What’s formed if (Y) acts on PIP2?

Answer 20

X = PLC
Y = PI3K (phosphoinositol 3 kinase)

Phosphorylated into PIP3, which interacts with PDKs (kinases) and Akt

Question 21

Gi(alpha) (activates/inhibits):

Answer 21

Inhibits AC and activates K channels

Question 22

List the categories of hormone receptors that have single transmembrane domains.

Answer 22

1. Tyr kinase
2. Ser/Thr kinase
3. Guanylate cyclase
4. Cytokine
5. MAP kinase

Question 23

Signal transduction of Tyr kinase receptors requires which steps?

Answer 23

1. Dimerization
2. Auto-phosphorylation of (cytoplasmic) Tyr residues
3. Associate with/phosphorylate substrates

Question 24

Signal transduction of Ser/Thr kinase receptors requires which steps?

Answer 24

1. Dimerization

2. Phosphorylation of Smads (cytoplasmic substrates)

Question 25

Smads are (membrane/cytoplasmic) substrates of (X) receptors. Upon activation via (Y), what is the function of Smads?

Answer 25

Cytoplasmic; X = Ser/Thr kinase Y = phosphorylation Enter nucleus and influence transcription of target genes

Question 26

(X) hormones are lipid-soluble and generally act by regulating (Y) in responsive cells.

Answer 26

``` X = steroid and thyroid (and vit A/D derivatives) Y = gene expression ```

Question 27

Receptors for steroid hormones are located in/on (X). The first thing that occurs when hormone binds is:

Answer 27

X = in cytoplasm Dissociation of associated proteins (which prevent inactivated receptors from interacting with DNA)

Question 28

Heat-shock proteins (i.e. HSP90) are associated with (X) receptors and function to (Y).

Answer 28

``` X = steroid Y = prevent inactivated receptors from interacting with DNA when ligand is absent ```

Question 29

Steroid binds its receptor and associated protein dissociates. What's the next step?

Answer 29

Dimerization of H-R complexes

Question 30

Steroid binds its cytoplasmic receptor and H-R dimer forms. List the next occurrences.

Answer 30

1. Translocate to nucleus 2. Interact with HREs (hormone response elements) on DNA 3. Initiate/suppress transcription of nearby genes

Question 31

HREs (hormone response elements) are (X) that have one of which characteristics?

Answer 31

X = DNA sequences 1. Palindromic sequences (inverted repeats) 2. Direct repeats

Question 32

T/F: Steroid, thyroid, and vit D/A derivative hormone receptors are typically bound to proteins that prevent their binding to DNA.

Answer 32

False - only steroid hormones (not the others)

Question 33

Thyroid hormone receptor: the inactive receptor is associated with (X) proteins that function to (Y).

Answer 33

``` X = nuclear Y = modulate transcription of downstream genes ```

Question 34

Thyroid hormone receptor: upon hormone binding, (X) changes causes (dissociation/attachment) of (Y).

Answer 34

``` X = conformational; Dissociation of (Y = nuclear proteins); AND attachment of other/different proteins ```

Question 35

Thyroid hormone receptor: when hormone binds, certain proteins associate with receptor and function to:

Answer 35

promote activation/suppression of transcription of target genes

Question 36

Intracellular receptors have which structural domains? Specify the function of each and star the highly conserved one(s).

Answer 36

1. C-term: hormone binding 2. Central: DNA binding* 3. N-term: transcription factor recruitment

Question 37

Intracellular receptors: the central, (X)-binding domain is rich in (Y) AA residues.

Answer 37

``` X = DNA Y = Cys ```

Question 38

Hormone-dependent responses of cells are affected by which two factors?

Answer 38

1. Availability of free hormone | 2. Sensitivity of cells to given hormone level

Question 39

Rates of (X) processes influence the amount of circulating free hormone.

Answer 39

X = secretion, uptake, and degradation

Question 40

T/F: An increase in carrier protein concentrations results in an increase in available, biologically active steroid/thyroid hormones.

Answer 40

False - reciprocal relationship (biologically active hormones are FREE, not bound)

Question 41

List the three main factors influencing cell sensitivity to given hormone.

Answer 41

1. Negative cooperativity 2. Down regulation of receptors 3. Other (i.e. uncoupling or enzyme inactivation)

Question 42

(X) is the phenomenon when binding of hormone to receptor decreases affinity of neighboring binding sites.

Answer 42

X = negative cooperativity

Question 43

Negative cooperativity may modulate hormone action by providing (high/low) cell sensitivity at (high/low) hormone concentrations.

Answer 43

High sensitivity at low concentrations and vice versa

Question 44

Uncoupling of receptor from (X) is one method that cells reduce sensitivity to hormones. This has been observed in (Y) system.

Answer 44

``` X = G-protein Y = beta-adrenergic ```

Question 45

T/F: Uncoupling of receptor to G-protein is done by de-phosphorylating the receptor's cytoplasmic domains.

Answer 45

False - phosphorylating (reduces its affinity for G-protein)

Question 46

Uncoupling: high hormone concentration means (more/less) (alpha/beta/gamma) domain at cell membrane. This means the potential for (X) kinase to be bound is (greater/less), increasing chance of receptor (activation/deactivation).

Answer 46

``` More; Beta-gamma X = beta-adrenergic receptor kinase (B-ARK) Greater; Deactivation ```