Cell responses to environment-Signals
Signal transduction can coordinate:
Responses to environment
Food (and other chemicals)
Light
Gravity
...
Development
Formation of tissues
Timing of cell division
Direction of cell enlargement
Size and shape of organs
“Structure of the human ß2adrenergic receptor (red)
embedded in a lipid
membrane and bound to a
diffusible ligand (green),
with cholesterol (yellow)
between the two receptor
molecules. A cartoon of
the lipidic cubic phase used
for crystalization of the
receptor is shown in the
background.”
(Control of enzyme activity
and gene expression
often involves receptors in
the plasma membrane.)
Receptors are proteins
•Polar and charged compounds have p.m. receptors
•Hydrophobic signals can have cytoplasmic receptors
Sodium
Insulin (a
protein)
Acetylcholine
Pressure
Estrogen
Cortisol
Light
“Transduction”: the events beween stimulus and response
Some signals involved in transduction steps:
Phosphorylation (kinases, phosphatases)
Voltage and ion transport across a membrane
Protein association/dissociation
GTP, GTP hydrolysis (G proteins)
Lipid metabolites (IP3: inositol triphosphate; DAG,
diacylglycerol)
Ca2+ (cytoplasmic concentration), calmodulin
cAMP, cGMP
NO
Kinases are important in eukaryotic signaling
Signal: insulin
Receptor: in
plasma membrane
Transduction:
change in receptor;
kinase activation;
phosphorylation
of target
Signal transduction can involve ion transport across a membrane
Opening of the
acetylcholine
receptor/sodium
channel allows
Na+ to enter a
muscle cell
Flow of sodium
changes the electric
field across the
membrane (less neg.
inside)
Voltage change opens
adjacent Na+ channels-amplification--and Ca2+
channels
Ca2+ stimulates actin-myosin association and contraction
Signal transduction can involve the release of an effector protein
Signal: cortisol
Receptor: bound to
chaperone
Transduction:
change in receptor
shape; release of
receptor; transcription
initiation
G proteins combine with GTP to form signals
In signal transduction, one signal often leads to another (“cascade”)
Signal:
growth factor
Receptor:
kinase
Transduction:
Ras (G protein);
Raf, MEK,
MAPk
(kinases);
transcription
Note GTP-GDP
exchange at
Ras
The hydrolysis of certain lipids generates signals
In signal transduction, one signal often leads to another
Receptor
G protein
P-lipase C
Ca2+ channel
Protein
kinase C
Note the lipid
metabolites
and Ca2+
Cyclic AMP is a common second messenger
(“second messenger”: intermediate in a signal cascade)
Cyclic AMP is involved in the release of glucose in the liver
Receptor
G protein
Adenylyl
Cyclase
cAMP
cascade of
kinases
Cyclic AMP is involved in the release of glucose in the liver
(Last kinase activates
phosphorylase
enzyme
directly, not enzyme
synthesis)
Notice the
signal
amplification
Cyclic AMP is involved in odor perception
Odorant/
receptor
activates
G protein
G protein
activates
adenylyl
cyclase
cAMP
opens ion
channels
(voltage
impulse)
NO is an example of a diffusable (long-distance) signal
G protein
IP3
Ca2+
NO synthase
cGMP
voltage
Summary: the types of signals are diverse
Phosphorylation (kinases, phosphatases)
Voltage across a membrane
Protein association/dissociation
GTP, GTP hydrolysis (G proteins)
Lipid metabolites (IP3:
inositol triphosphate; DAG,
diacylglycerol)
Ca2+
(cytoplasmic concentration), calmodulin
cAMP, cGMP
NO
Summary: the effects of signals are diverse
 Transcription: new mRNAs and proteins
 Activation of enzymes
 Opening of ion channels
How can a few types of signals coordinate so many
processes?
Combinations: some signals work on multiple targets
Combinations: some targets need multiple signals
Differentiation: signals trigger functions in prepared cells
Neves, Science 296:1136, 2002
A recent article in Science identifies similar signal
cascades in taste cells and respiratory tissues.
Can you identify the signals?
Kinnamon and Reynolds, Science 325:1081, 2009