Module 5 Flashcards
(36 cards)
1
Q
signaling by secreted molecules
A
- signaling cell releases signaling molecules via exocytosis
- signaling molecules bind to the receptor on the target cell
- most common
2
Q
signaling by plasma-membrane bound molecules
A
- signaling molecule remains tightly bound to the plasma membrane of the signaling cell
- signaling cell makes contact with the target cell
- signaling molecule binds to the receptor
- more rare
3
Q
hydrophilic signaling molecules
A
often interact with the target membrane through cell surface receptors
4
Q
hydrophobic signaling molecules
A
- use intracellular receptors
- need to pass through the plasma membrane in order to encounter their receptors
- carrier protein shields the signaling molecule from the aqueous environment
5
Q
gap junctions
A
- formed between the plasma membranes of two opposing cells
- contain a small pore where signaling molecules can pass through
- ex: Ca2+, cAMP
6
Q
acetylcholine
A
- an example of a signaling molecule (neurotransmitter)
- induces contraction in skeletal muscle
- induces relaxation in heart muscle
- induces secretion in some secretory cells
7
Q
paracrine signaling
A
short range
8
Q
synaptic signaling
A
- long range
- neurotransmitter released from the axon of a nerve cell and received by the target cell
- axons are very long
9
Q
endocrine signaling
A
- long range
- endocrine cell releases a hormone that can enter the bloodstream, exit the bloodstream at a further distance, and reach target cells
10
Q
autocrine signaling
A
- short range
- signaling cells can communicate with the same type of cells or even themselves
11
Q
3 groups of hydrophobic signaling molecules
A
steroids, thyroid hormones, retinoids
12
Q
steroids
A
- all synthesized from cholesterol
- ex: cortisol, estradiol, testosterone, vitamin D
13
Q
thyroid hormones
A
- often made from thyrosine
- increase metabolism in many cell types
- ex: thyroxine
14
Q
retinoids
A
- play a role in vertebrate development
- ex: retinoic acid
15
Q
3 domains of intracellular receptors
A
activation domain, ligand binding domain, inhibitory protein complex
16
Q
activation domain of intracellular receptor
A
N terminus
17
Q
ligand binding domain of intracellular receptor
A
where hormone or hydrophobic signaling molecule binds
18
Q
inhibitory protein complex of intracellular receptor
A
- Hsp90 (chaperone)
- blocks the DNA binding domain
- keeps the receptor inactive until the steroid binds
- when the steroid binds, Hsp90 leaves and the DNA binding domain is exposed
- the receptor then travels to the nucleus
19
Q
early primary response of intracellular receptors
A
- Steroid hormone interacts with steroid receptor
- Receptor-hormone complex enters the nucleus
- Receptor-hormone complex can bind to specific regions of DNA to increase transcription and translation of different proteins
20
Q
secondary response of intracellular receptors
A
- some act in a negative feedback loop and turn off transcription of primary response genes
- some behave as transcription factors and enhance transcription and translation of secondary response proteins
21
Q
relay system
A
- used for hydrophilic signaling molecules
- gets the signal from the receptor to the nucleus
- one protein becomes activated, which activates a second protein, then a third protein, etc.
22
Q
2 ways for proteins to become activated
A
- phosphorylation
- binding of GTP
23
Q
G-protein linked receptors
A
- aka G-protein coupled receptors
- bind ligand and interact with a heterotrimeric G-protein
- 7 pass transmembrane proteins
- have a ligand binding domain in the extracellular space
- have a G-protein binding domain in the cytosol
- C3 loop is important for specificity
- regulate levels of cAMP
24
Q
stimulatory G-proteins (Gs proteins)
A
- activate adenylyl cyclase
- results in an increase in cAMP
25
inhibitory G-proteins (Gi proteins)
- inhibit adenylyl cyclase
| - result in a decrease in cAMP
26
cAMP
- second messenger
| - made from ATP through the action of adenylyl cyclase
27
process of Gs protein-coupled receptor
1. Ligand binds to Gs protein-coupled receptor in the plasma membrane
2. Gs protein-coupled receptor binds to Gs protein
3. Gs protein exchanges GDP for GTP to become activated (GTP binds to the alpha subunit of the Gs protein)
4. The alpha subunit is now activated and diffuses away from the beta and gamma subunits of the Gs protein
5. The alpha subunit interacts with adenylyl cyclase to activate it
6. Adenylyl cyclase converts ATP to cAMP
7. Hydrolysis of GTP to GDP in the alpha subunit causes it to dissociate from adenylyl cyclase and bind back with the beta and gamma subunits
28
How was FRET used to see how fast the alpha subunit dissociates?
- YFP was placed on the beta and gamma subunits of the G protein
- CFP was placed on the alpha subunit of the G protein
- if all 3 subunits are together, you should see yellow light
- if the alpha subunit is dissociated, you should see blue light
- alpha subunit dissociates within 10-15 sec
29
stimulatory hormones
epinephrine, glucagon, ACTH
30
inhibitory hormones
PGE, adenosine
31
What determines whether the G protein-coupled receptor binds to a Gs or Gi protein?
the C3 loop of the receptor
32
protein kinase A (PKA)
- can phosphorylate other proteins
- has 2 catalytic subunits and 2 regulatory subunits
- when all 4 subunits are together, PKA is inactive
- when cAMP binds to the regulatory subunits, the catalytic subunits are released and PKA is activated
33
What happens downstream of PKA?
- glycogen breakdown in muscles
- alterations in transcription
- release of fluid across epithelial cells
34
glycogen breakdown in muscles downstream of PKA
1. cAMP binds to the regulatory subunits of PKA to activate it
2. Activated PKA phosphorylates (and therefore activates) phosphorylase kinase via ATP hydrolysis
3. Activated phosphorylase kinase phosphorylates (and therefore activates) glycogen phosphorylase via ATP hydrolysis
4. Glycogen phosphorylase converts glycogen to glycogen 1-phosphate which can enter glycolysis to make ATP
35
changes in gene expression downstream of PKA
1. Ligand binds to Gs protein-coupled receptor
2. Adenylyl cyclase is activated
3. cAMP accumulates
4. cAMP activates PKA
5. Catalytic subunits of PKA enter the nucleus to phosphorylate CREB (cAMP response element binding protein)
6. Phosphorylated CREB binds to cAMP responsive elements (CRE) in the promoters and enhancers of a wide variety of genes
7. CREB attracts CBP/P300 which binds to CREB and the basal transcription machinery
8. CREB and CBP/P300 form a powerful transcriptional activation complex that can induce the transcription of a wide variety of genes
36
release of fluid across epithelial cells downstream of PKA
1. cAMP binds to the regulatory subunits of PKA
