Intracellular Signalling at the Cell Membrane Flashcards
the intracellular events that transform the extracellular signal into an intracellular signal
transduction
examples of effectors
protein kinases or transcription factors
An extracellular signal activates a ________
membrane-bound receptor
receptor activation leads to an _______ cytosolic or membrane concentration of 2nd messenger
increased
Single activated receptor → many molecules of 2nd messenger =
amplification
signal termination is due to a number of processes (3)
- inactivation of receptor (no 1st messenger) or receptor-associated effectors
- degradation or removal of 2nd messenger
- negative feedback
name 3 types of cell membrane receptors
- ion channel-coupled receptors
- G-protein coupled receptors
- enzyme-coupled receptors
the largest family of cell membrane receptors are
G-protein-coupled receptors (GPCRs)
800 unique G-protein-coupled receptors (GPCRs). Almost half of ________ act on these receptors or their pathways
medications
GPCR: Receptor activation → activation of a protein that binds to a _____ nucleotide
guanine
The activated G-protein is on a “timer”. Has intrinsic GTP-ase activity. When GTP hydrolyzed → GDP then the G-protein is
______
inactive
Receptor = integral transmembrane protein. Spans the membrane _ times
7
3 protein subunits:
α, β, γ
α is bound to GDP, and βγ is bound to α
unstimulated
α subunit releases GDP, replacing it with GTP and the α subunit disengages from the βγ subunits
Stimulated
When the α unit hydrolyzes
GTP → GDP, it becomes
______ again
inactivated
- Ligand binds to receptor associated with a ___ G-protein
- G_ releases GDP and binds GTP at the alpha subunit - by detaches from G-protein
- G_ binds to and activates adenylyl cyclase
- membrane-bound enzyme that converts ATP to cAMP - cAMP binds to protein kinase (PK A)
- binds to inhibitors of PK A, which then detach, and allow the activate parts of PK A to work - PK A phosphorylates a multitude of effector proteins
Gs GPCR
what enzyme converts ATP to cAMP
adenylyl cyclase
what enzyme causes an inactivation of cAMP by converting it to 5’-AMP
cyclic AMP phosphodiesterase
- called the “turning off” process
Stimulates adenylyl cyclase → cAMP production. cAMP activates PK A → phosphorylation of effectors
Gs
biological impact of: Glycogenolysis,
thyroid hormone
synthesis
Gs
alpha subunit Inhibits adenylyl
cyclase → decreased cAMP production. Decreases PK A activation.
Gi
what pathway inhibits Gs pathways
Gi alpha
beta-gamma Activates K+ channels*. Creates More negative cell membrane potential.
Gi
Biological impact of reduction of
heart rate
Gi beta-gamma
Activates phospholipase C → IP3 and DAG production. IP3 → calcium release
from ER. DAG → activation of
BK C
Gq (a)
Activates cGMP phosphodiesterase → decreased cGMP. Decreased cGMP → closes Na+ channels → more negative cell membrane potential.
Gt (a)
biological impact: Detection of light
– rod photoreceptors in retina
Gt (a)
IP3 is a 2nd messenger that has one effect →
it causes release of Ca+2 from where it’s stored in the endoplasmic reticulum (ER)
Ca+2 has many effects – it can bind to and activate a number of proteins
modulation of a very large range
of effectors
Good example of a Ca+2–binding protein:
calmodulin
A “resting” cell (no calcium signal) has ___ micromolar of Ca+2 in the cytosol, and ____ mmol of calcium in the endoplasmic reticulum and in the extracellular space
0.1 micromolar and 1-3 mmol
The concentration gradient for calcium for is very high → it ____ to enter the cytosol
“wants”
A cell that is “activated” can reach Ca+2 concentrations of __ micromolar or more
10 mm
When the concentration of Ca+2 ___ in the cytosol, then it will bind to calcium-binding proteins in the cytosol → an effect
increases
Each calmodulin binds to ____ Ca+2 ions before it becomes activated
four
IP3 is water soluble – it enters the
cytosol
DAG is lipid soluble – it stays within the ________ and diffuses throughout it
cell membrane
This is a ubiquitous inhibitory G-protein that
downregulates the activity of Gs
Gi
Opening of K+ channels brings the cell closer to its Nernst potential for K+. What is the nernst potential of K+
-90mV
what does a very negative membrane potential cause?
it tends to cause most cells to be “less” activated
What would be the impact on the membrane potential if sodium enters the cell?
Makes the membrane potential more positive
If the channel allows sodium to enter → the membrane becomes more “inside-positive. This is known as ___________
depolarization
If the channel allows more potassium to leave → the membrane becomes more “inside-negative”. This is known as __________
hyperpolarization
T or F: Making the membrane more inside-positive or more inside-negative impacts the activation of certain membrane-associated proteins
True
Making the membrane more inside-positive or more inside negative impacts the activation of certain membrane-associated proteins
intrinsic kinase activity
The binding of ligand ________ the receptor and
activates a tyrosine kinase within the receptor
dimerizes
Ligand examples of RTKsgand examples
▪ Insulin
▪ Growth factors
▪ Cytokines
what is a pathway that does not produce 2nd messengers?
RAS-RAF-MAP
which system is our KEY insulin signalling system
PI-3-Kinase (PI3K) > Akt System
nitric oxide synthase (NOs) on L-arginine
creates Nitric Oxide
- a small molecule that rapidly degrades as it is a free radical
what causes the activation of nitric oxide synthase (NOs)
an increase of cytosolic calcium
Na in the cell is
low
potassium in the cell is
high
calcium in the cell is
low
Transmembrane proteins with ligand-binding
domain on the outer surface of the plasma membrane are called:
enzyme-coupled receptors
Binding of ligand ______ the receptor and
activates a tyrosine kinase within the receptor
dimerizes
ligand examples of RTK
- insulin
- growth factors
- cytokines
what is Ras-Raf-MAP kinase key for:
growth factors
_____ is a key mediator that relaxes smooth
muscle in a wide variety of blood vessels and visceral organs
Nitric oxide
Very small, hydrophobic gas that _____ and quickly through cell membranes
diffuses easily
▪ It’s a second messenger – one of the only ones that can diffuse across the cell membrane and impact other cells
Nitric Oxide
