01a: Hormone-Receptor Interactions Flashcards
T/F: All hormones, to initiate a response, must bind to receptors on target cells.
False - receptors can be inside target cell
T/F: Hormone-Receptor Interaction has both high specificity and high affinity.
True
T/F: Hormone-Receptor interaction, in many cases, is a simple, unimolecular, reversible reaction.
False - simple, bimolecular, reversible
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).
KA;
KD (reciprocal of KA)
Low
T/F: Frequently, the H-R interaction is defined by its KA.
False - by its KD
If the free hormone concentration is equal to KD, what does that tell you about the receptors?
Half are occupied/bound
In order to have about 90% occupancy of hormone receptors, (X) should be increased (Y)-fold over (Z).
X = free hormone concentration Y = 10 Z = KD
If there’s about 10% occupancy of hormone receptors, (X) must be (Y)-fold greater than (Z).
X = KD Y = 10 Z = free hormone concentration
(or free hormone concentration is 1/10 of KD)
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.
True
T/F: Upon release of a hormone, the hormone-receptor interaction occurs in all tissues.
False - only responsive tissues (sensitive to that hormone)
Hormones that are derivatives of (X) are too polar to pass through (Y) and too large to pass through (Z).
X = peptides and amines Y = lipoprotein membranes (diffusion) Z = membrane pores
List the two general groups of (membrane/cytoplasmic) receptors for water-soluble hormones.
Membrane;
- Serpentine (7 membrane-spanning domains)
- Single membrane-spanning domains
G-proteins are hetero-(dimers/trimers/tetramers). Alpha-subunit is a(n) (X) and is predominantly bound to (Y).
Hetero-trimer;
X = GTPase
Y = GDP, beta-gamma subunit, and receptor
Gs(alpha) is a (stimulatory/inhibitory) protein for (X), which (activates/forms/inhibits) (Y), which (activates/inhibits/forms) (Z).
Stimulatory; X = AC Forms; Y = cAMP (from ATP) Activates; Z = PKA
Describe the exact mechanism by which cAMP activates PKA.
Binds regulatory subunits and causes dissociation of active, catalytic subunits from the complex
T/F: PKA has multiple substrates, all of which are in the cytoplasm.
False - can also affect transcription of target genes in nucleus
Gq(alpha) (activates/inhibits) (X), which target/action?
Activates;
X = PLC
Cleaves PIP2 (into IP3 and DAG)
IP3 is formed by (X) with which function?
X = cleavage of PIP2
Mobilizes Ca from vesicular storage
DAG is formed by (X) with which function?
X = cleavage of PIP2
Activates PKC in the presence of Ca
PIP2 can either be cleaved by (X) or acted on by (Y). What’s formed if (Y) acts on PIP2?
X = PLC Y = PI3K (phosphoinositol 3 kinase)
Phosphorylated into PIP3, which interacts with PDKs (kinases) and Akt
Gi(alpha) (activates/inhibits):
Inhibits AC and activates K channels
List the categories of hormone receptors that have single transmembrane domains.
- Tyr kinase
- Ser/Thr kinase
- Guanylate cyclase
- Cytokine
- MAP kinase
Signal transduction of Tyr kinase receptors requires which steps?
- Dimerization
- Auto-phosphorylation of (cytoplasmic) Tyr residues
- Associate with/phosphorylate substrates
Signal transduction of Ser/Thr kinase receptors requires which steps?
- Dimerization
2. Phosphorylation of Smads (cytoplasmic substrates)
Smads are (membrane/cytoplasmic) substrates of (X) receptors. Upon activation via (Y), what is the function of Smads?
Cytoplasmic;
X = Ser/Thr kinase
Y = phosphorylation
Enter nucleus and influence transcription of target genes
(X) hormones are lipid-soluble and generally act by regulating (Y) in responsive cells.
X = steroid and thyroid (and vit A/D derivatives) Y = gene expression
Receptors for steroid hormones are located in/on (X). The first thing that occurs when hormone binds is:
X = in cytoplasm
Dissociation of associated proteins (which prevent inactivated receptors from interacting with DNA)
Heat-shock proteins (i.e. HSP90) are associated with (X) receptors and function to (Y).
X = steroid Y = prevent inactivated receptors from interacting with DNA when ligand is absent
Steroid binds its receptor and associated protein dissociates. What’s the next step?
Dimerization of H-R complexes
Steroid binds its cytoplasmic receptor and H-R dimer forms. List the next occurrences.
- Translocate to nucleus
- Interact with HREs (hormone response elements) on DNA
- Initiate/suppress transcription of nearby genes
HREs (hormone response elements) are (X) that have one of which characteristics?
X = DNA sequences
- Palindromic sequences (inverted repeats)
- Direct repeats
T/F: Steroid, thyroid, and vit D/A derivative hormone receptors are typically bound to proteins that prevent their binding to DNA.
False - only steroid hormones (not the others)
Thyroid hormone receptor: the inactive receptor is associated with (X) proteins that function to (Y).
X = nuclear Y = modulate transcription of downstream genes
Thyroid hormone receptor: upon hormone binding, (X) changes causes (dissociation/attachment) of (Y).
X = conformational; Dissociation of (Y = nuclear proteins); AND attachment of other/different proteins
Thyroid hormone receptor: when hormone binds, certain proteins associate with receptor and function to:
promote activation/suppression of transcription of target genes
Intracellular receptors have which structural domains? Specify the function of each and star the highly conserved one(s).
- C-term: hormone binding
- Central: DNA binding*
- N-term: transcription factor recruitment
Intracellular receptors: the central, (X)-binding domain is rich in (Y) AA residues.
X = DNA Y = Cys
Hormone-dependent responses of cells are affected by which two factors?
- Availability of free hormone
2. Sensitivity of cells to given hormone level
Rates of (X) processes influence the amount of circulating free hormone.
X = secretion, uptake, and degradation
T/F: An increase in carrier protein concentrations results in an increase in available, biologically active steroid/thyroid hormones.
False - reciprocal relationship (biologically active hormones are FREE, not bound)
List the three main factors influencing cell sensitivity to given hormone.
- Negative cooperativity
- Down regulation of receptors
- Other (i.e. uncoupling or enzyme inactivation)
(X) is the phenomenon when binding of hormone to receptor decreases affinity of neighboring binding sites.
X = negative cooperativity
Negative cooperativity may modulate hormone action by providing (high/low) cell sensitivity at (high/low) hormone concentrations.
High sensitivity at low concentrations and vice versa
Uncoupling of receptor from (X) is one method that cells reduce sensitivity to hormones. This has been observed in (Y) system.
X = G-protein Y = beta-adrenergic
T/F: Uncoupling of receptor to G-protein is done by de-phosphorylating the receptor’s cytoplasmic domains.
False - phosphorylating (reduces its affinity for G-protein)
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).
More; Beta-gamma X = beta-adrenergic receptor kinase (B-ARK) Greater; Deactivation
