3. Receptors and Cell Signaling Flashcards
Where are the receptors for hydrophilic signaling molecules invariably located?
On the exterior of the plasma membrane.
What is the example given for Endocrine signaling?
Epinephrine (Short acting - despite what the slide says)
What is the example given for Paracrine signaling?
Testosterone
What is the example given for Autocrine signaling?
Interleukin-1
What is the example given for Direct / Juxtacrine signaling?
Heparin-binding epidermal growth factor
What are the seven steps of the trimeric G Protien signal relay?
- Ligand binds
- Conformational change
- GPCR binds to G Protien
- GPCR acts as a GEF (Guanidine Exchange Factor)
- Galpha trades its GDP for GTP
- Activated Galpha activates or inhibits effector molecule
- The effector molecule catalyzes the reaction!
What intrinsic portion of the G Protein hydrolyses GTP to GDP to turn itself off?
What subunit houses this activity?
intrinsic GTPase
alpha subunit
Trimeric G Protiens will eventually release GTP and turn back off, but what enzyme makes this trade happen faster?
GTPase Activating protien
What is the function of the Gs G protien?
What second messenger is released as a result?
What enzyme does this second messenger activate?
And what does THAT thing do?
Simulation of Adenylate Cyclase
cAMP
PKA
Phosphorylates a target protien.
What is the function of the Gt G protien?
What does that protien do?
What type of signaling is this?
Stimulation of cGMP phosphodiesterase
Catalyzes the elimination of cGMP
Negative signaling (cGMP does something, but this mechanism stops it)
The T in Gt means “Turn off the light!”
What is the function of the Gi G protien?
What is the result?
Inhibition of adenylate cyclase
cAMP is not produced, and PKA is not activated.
- What is the function of the Gq G protien?
- What happens as a result? (2 things)
- What enzyme is activated, and what second messenger is released?
- Activates phospholipase C
- PIP is turned into IP3 and DAG
- IP3 opens a Calcium channel
- DAG and calcium activate PKC
- Calcium + Calmodulin is released to influence other protiens.
What signal molecules use Gs?
Epinephrine (using beta-adrenergic receptors)
Histamine
I get Scared (epinephrine) by Bees (beta adrenergic) ‘cause I’m allergic (histamine), so I’m Gonna Scream (Gs)
What signal molecules use Gi?
Epinephrine (using an alpha-adrenergic receptor)
Dopamine
Say _no (_inhibitor) to dope (dopamine), even if it’s scary (epinephrine), then you’ll be the alpha
What signal molecules use Gq?
Acetylcholine
Stylish men train their muscles
_(_GQ is a men’s style magazine, acetylcholine activates muscles)
What signal uses Gt?
Light
- Turn off the light!*
- Gt triggers cGMP phosphodiesterase to turn the cGMP signal off.*
How does caffeine affect the heart?
It inhibits cAMP PDE
cAMP increases heart rate, and cAMP PDE gets rid of cAMP. Since caffeine stops cAMP PDE from getting rid of cAMP, cAMP stays high, and heart rate does too.
Why are ED meds contraindicated in patients taking nitrates?
NO (nitrates) increase cGMP production to increase vasodilation
ED meds inhibit the breakdown of cGMP, effectively raising the concentration as well.
The combination of the two cGMP increasing factors can result in deadly drops in blood pressure!
For Cholera
What G protien and subunit is affected?
What is changed on this protein?
What is overproduced as a result?
What causes the symptoms?
Gs alpha subunit
It has decreased GTPase activity
Gs alpha is stuck on, stimulating Adenylate Cyclase to be stuck on as well.
cAMP is overproduced
Cl- channels are left open, causing electrolyte and water loss.
For pertussis
What G protien and subunit is affected?
What happens to the G protien?
What happens as a result?
Gi alpha subunit
Ribosylation prevents alpha subunit dissociation (part of activation)
Since Gi is in charge of stopping adenylate cyclase, AC is left on and too much cAMP is produced. Fluid and mucous floods the airway.
What do G protein receptor kinases (GRKs) do?
How do they do it? (and what other protien helps?)
Where does this happen?
The inactivate G Protein coupled receptors (GPCRs)
They phosphorylate the GPCR, then an arrestin protien binds and prevents conformational change so that GDP cannot become GTP
The 3rd intracellular loop (cytosolic side)
For Receptor Tyrosine Kinases (RTK’s)
What happens after the signal binds? (2)
Where do the intracellular adapter / docking protiens bind?
The receptor dimerizes and autophosphorylates
To the phosphorylated Tyrosine residues
After a Receptor Tyrosine Kinase becomes phosphorylated and recruits its adapter and docking protiens, what two pathways can it use to trigger the protien targets?
Which one uses MAPK?
What is MAPK?
RAS-dependent - uses MAPK
RAS independent
A monomeric G Protein
What is the clinical relevance of RAS or its separate GEFs?
They have been implicated in a wide range of cancers.
