Intracellular Signaling at the Cell Membrane Flashcards
Receptors in the cell membrane are key in what 2 functions?
Detecting extracellular signals and modifying cell function based on those signals
What are the intracellular events that transform the extracellular signal into an intracellular signal?
Transduction
What do these events all involve?
-Source of some 2nd messengers
-Site where some 2nd messengers accumulate
-Site where ionic 2nd messengers are regulated
- Important site where regulatory proteins and enzymes localize and integrate signaling
The cell membrane
Describe the initial activation intracellular signaling model.
Ligand Binding: A signaling molecule (ligand) attaches to a cell membrane receptor.
Receptor Activation: This binding activates the receptor.
Intracellular Protein Activation: The activated receptor triggers an intracellular protein.
Second Messenger Production: This protein generates a second messenger.
Second Messenger Activation: The second messenger activates another protein.
Signaling Cascade: This protein sets off a series of reactions.
Cellular Effects: The cascade leads to cellular responses or changes.
What is an effector?
A cellular component that carries out specific actions in response to a signal.
What’s another name for the first messanger?
Lignan
Describe the deactivation of the intracellular signaling model.
Decreased First Messenger: When the concentration of the first messenger decreases,
Inactive Receptor: The cell membrane receptor is no longer activated.
Inactive Protein: The protein associated with the receptor becomes inactive.
Second Messenger Depletion: The protein or enzyme stops producing the second messenger.
Second Messenger Inactivation: Another mechanism reduces or inactivates the second messenger.
Ineffective Activation: With the low second messenger concentration, it can’t activate its target protein.
Inactive Effectors: Effectors are no longer activated.
What’s another term for deactivation?
Downregulation
Why does downregulation take place?
To prevent overstimulation or maintain a balance in cellular signaling.
What is the extracellular signal known as?
First messenger
What happens during receptor activation?
An increased cytosolic or membrane concentrations of a 2nd messenger
What is the process by which a relatively small initial signal or stimulus is greatly increased in magnitude or effect as it progresses through a signaling pathway
Amplification
What are 3 reasons for signal termination?
Inactivation of receptor (i.e. no 1st messenger) or receptor-associated effectors
degradation or removal of 2nd messenger
negative feedback
What are 3 types of cell membrane receptors?
1.) Ion channel-coupled receptors
2.) G-protein-coupled receptors
3.) Enzyme-coupled receptors
Which is the largest family of cell membrane receptors?
G-protein-coupled receptors (800)
Almost half of medications act on what receptors/pathways?
G-protein-coupled
What is a G-protein?
Guanine nucleotide
True or False. The activated G-protein will modify the activity of an enzyme.
True.
Does the activation G-protein have intrinsic GTP-ase activity? Or does it get its energy elsewhere?
Intrinsic
When GTP hydrolyzed
into GDP, what happens?
Then the G-protein is inactive
What are the 3 G-protein subunits?
alpha, betta, gamma
How are the g- protein subunits bound: Unstimulated?
α is bound to GDP, and βγ is bound to α
How are the g- protein subunits bound: Stimulated?
α subunit releases GDP, replacing it with GTP and the α subunit disengages from the βγ subunits
What happens when α unit hydrolyzes GTP into GDP?
It becomes inactivated again
Gs binds to and activates _______________.
This membrane-bound enzyme that converts ATP to _________.
adenylyl cyclase, cAMP
(Gs) cAMP binds to which enzyme?
Protein kinase A (PKA)
What does PKA phosphorylate?
A multitude of effector proteins
CREB is an important target protein that ________ phosphorylates.
PKA
Adenylyl cyclase catalyzes the conversion of what? To what?
The conversion of ATP to cAMP
What enzyme catalyzes the inactivation of cAMP? The turning off process?
Cyclic AMP phosphodiesterase
True or False.
Sometimes βγ subunits activate effectors on their own, without “using” a 2nd messenger
True. During Gi and Gq
Which GPCR uses Ca+2 and IP3 and DAG as 2nd messenger systems
Gq
Which 2nd messenger that has one effect? It causes release of Ca+2 from where it’s stored in the endoplasmic reticulum (ER).
IP3
Which Gq second messenger system has many effects, it can bind to and activate a number of proteins and modulation of a very large range of effectors
Ca2+
(Gq)What second messenger system does Ca2+ bind to?
Calmodulin
(Gq)How much more increase in Ca2+ concentrations is there in a cell that is “activated” rather than inactive?
100X increase. Can reach Ca+2 concentrations of 10 micromolar or more.
(Gq)What happens when the concentration of Ca+2 increases in the cytosol?
It will bind to calcium-binding proteins in the cytosol and an effect will take place.
Each calmodulin binds to how many Ca+2 ions before it becomes activated?
4
True or False. Once calmodulin is activated, it can bind to effectors.
True
After a ligand binds to a receptor associated with a Gq G-protein, Gq-alpha activates ____________.
phospholipase C
What does phospholipase C do?
It cleaves a membrane lipid into IP3 and diacylglycerol (DAG)
What is the membrane lipid in the Gq GPCR?
PIP2
(Gq) Once cleaved, _______ is water soluble – it enters the cytosol
IP3
(Gq) Once cleaved, ________ is lipid soluble – it stays within the cell membrane and diffuses throughout it
DAG
(Gq)IP3 activates a ________release channel in the ER
Ca+2
(Gq) Both Ca+2 and DAG work together to activate membrane-bound protein __________
kinase C (PK C)
What in the inhibitory G-protein that downregulates the activity of Gs?
Gi
What does Gi alpha inactivates?
adenylyl cyclases
What does Gi-βγ open?
K+ channels
What does opening of K+ channels do?
Brings the cell closer to its Nernst potential for K+
What is the Nernst potential for K+
-90 mV
By having a very negative membrane potential, what tends to happen?
It tends to cause most cells to be “less” activated.
Calcium concentrations inside the cell are almost ________ times (lower/higher) than outside the cell at rest
10,000/lower
In ion channels, if the channel allows sodium to enter, the membrane becomes more “inside (positive/negative)”?
What is this known as?
Positive/depolarization
If the channel allows more potassium to leave, the membrane becomes more “inside positive/negative”?
What is this known as?
Negative/hyperpolarization
