Chapter 5/Cell Signaling in Physiology Flashcards
Chemical messengers bind to
receptor
Water-soluble messengers bind to receptors
located at the
plasma membrane
Lipid-soluble messengers bind to
intracellular
receptors
cells express different receptors
Specificity
strength of ligand-receptor binding
Affinity
Different cells can have different responses to same
ligand
Specificity: cells express different receptors.
High affinity will bind at lower concentrations of
messenger
Affinity: strength of ligand-receptor binding
the fraction of total binding sites
that are occupied
Saturation
presence of multiple ligands able
to bind the same binding site
Competition
blocks the action of a chemical
messenger
Antagonists
activates receptors and triggers the cell’s
response
Agonist
receptors are removed
(internalized) in response to intense exposure to chemical messengers.
Down-regulation
number of receptors is
increased in response to low concentrations of
chemical messengers
Up-regulation
Up-regulation & down-regulation
Receptor Regulation
Can diffuse through the plasma membrane.
– Have intracellular receptors.
– Signal-receptor complexes bind directly to DNA
and alter gene expression.
– Slower response, but sustained response
Lipid-soluble messengers
A broad range of receptors.
– Activate intracellular signaling cascades
– Can activate mediators that affect DNA
expression
– Faster response but less sustained.
– Involve first messengers and second messengers
Membrane-bound receptors
Lipid-soluble messengers,
Membrane-bound receptors
Signal Transduction Pathways
Activation of receptor results in open ion
channel.
* Opening of ligand gated ion channels increase
net diffusion of ions specific to channel.
* Often results in a change in the membrane
potential.
* Ex: Na+, K+, Ca2+
Ligand-Gated Ion Channels
Some receptors have intrinsic
enzyme activity
Most are protein kinases that phosphorylate
the amino acid tyrosine
Receptor tyrosine kinase
transferring a phosphate
group from ATP
Phosphorylation
Binding of messenger to
receptor activates
enzymatic portion of
receptor.
* This autophosphorylates
the receptor’s tyrosine
groups
* Docking proteins bind to
phosphorylated tyrosine
groups.
* Activate cell’s response
Events for receptors with tyrosine kinase activity
These receptors do not have intrinsic kinase activity
Cytoplasmic Kinases
Binding of ligand causes conformational
change in receptor that leads to activation of
JAK kinase
-Family of 4 kinases, target different transcription
factors.
–Results in synthesis of new proteins.
Cytoplasmic Kinases
Receptor with inactive protein complex bound to it.
G Proteins
3 subunits: alpha, beta, gamma.
– Alpha subunit can bind GDP and GTP.
– Beta and gamma subunits anchor alpha subunit to
the membrane
G-Proteins
Binding of ligand to receptor changes
conformation of the receptor.
– Activated receptor increases the affinity of alpha subunit for GTP
– Alpha subunit binds GTP and dissociates from the
beta and gamma subunits.
– Alpha subunit binds to effector protein in plasma
membrane.
Steps
G protein serves as a BLANK coupling a
receptor to an ion channel or to an enzyme
SWITCH
Can be stimulatory or inhibitory
G Protein-Coupled Receptors
Most numerous type of receptor family, large
variety of signaling pathways
G Protein-Coupled Receptors
Adenylyl Cyclase
Second Messengers
Activated by stimulatory G proteins
– Catalyzes the conversion of ATP to cyclic AMP
(cAMP)
– cAMP acts as a second messenger
Adenylyl Cyclase
cAMP action
Second Messengers
cAMP action is terminated by cAMP BLANK
phosphodiesterase
-Breaks down cAMP
– Inhibition of cAMP phosphodiesterase prolongs
actions of cAMP
Second Messengers
cAMP binds to
-PKA phosphorylates downstream targets
cAMP-dependent protein
kinase (PKA
Some G proteins inhibit
Results in less generation of cAMP
adenylyl cyclase
activated by Gq,
catalyzes breakdown of a phospholipid (PIP2)
-second messengers
Phospholipase C (PLC)
- Diacylglycerol (DAG)
– Inositol Triphosphate (IP3)
– Both function as second messenger
Phospholipase C (PLC
DAG activates
protein kinase C
IP3 binds to ligand gated Ca2+ channels in
ER
Ca2+ as
Secondary Messenger
Ca2+ can be increased or decreased to elicit a
cellular response
action potential
Ca2+ is maintained at BLANK concentration in the
cell
Low
Electrochemical gradient favors diffusion into the
cytosol via
Ca2+ channels
Cell can be altered by influencing active
transport systems of
Ca2+
– Calmodulin
– Troponin
– Kinases
Ca2+ also acts by binding proteins and
activating them
Ca2+ as
Secondary Messenger
Ca2+ also acts by
binding proteins and
activating them
Signal transduction pathways are eventually
shut off
-Cessation of receptor activation
-Decrease in concentration of first messenger
Cessation of Activity
-Receptor become chemically altered
– Phosphorylation of receptor prevents further G
protein binding to the receptor
– Plasma membrane receptors may be removed
Receptors can be inactivated in 3 ways
Signal pathways do not exist in isolation, they
occur simultaneously.
* Many first messengers may simultaneously
influence a cell.
* “Cross-talk” can occur at one or more levels
among signal transduction pathways.
Interactions of Signal Transduction Pathways
Signal pathways do not exist in isolation, they
occur BLANK
simultaneously
Many BLANK messengers may simultaneously
influence a cell.
first
can occur at one or more levels among signal transduction pathways
Cross-talk
