Receptor Transduction
Mechanisms
Jenafer Evans, University of Florida, Gainesville, Florida, USA
Colin Sumners, University of Florida, Gainesville, Florida, USA
Craig H Gelband, University of Florida, Gainesville, Florida, USA
Neurotransmitter and peptide signalling requires receptor-mediated responses to affect
the target cell. General principles of ionotropic and metabotropic receptor-mediated
signalling include membrane potential alterations, calcium signalling, and kinase activity.
Introduction
For cells to function together in an organism, they must
have a means of communicating and coordinating growth,
differentiation, metabolism, and even death. Some signal
molecules, like steroids or nitric oxide, can diffuse through
lipid bilayers freely. Other signal molecules depend on
receptor proteins on the cell surface to transduce their
message across the cell membrane. These signals, called
ligands, bind specifically to their receptors with high
affinity, causing a conformational change in the receptor.
Agonists mimic the endogenous ligand while antagonists
bind with high affinity to and prevent activation of the
receptor.
There are two major mechanisms by which the signal
crosses the membrane once it has activated the receptor.
Metabotropic receptor activation involves second messen-
gers on the intracellular side while stimulation of ligand-
Agonist
Ions
Metabotropic
Ionotropic receptor
receptor
2nd messenger
Ions
molecules
Target
enzymes
Cellular
events
Figure 1 Two distinct types of neurotransmitter receptors. Metabotropic
receptor activation requires second messengers on the intracellular side.
Stimulation of an ionotropic receptor allows passage of ions through the
receptor itself.
ENCYCLOPEDIA OF LIFE SCIENCES © 2001, John Wiley & Sons, Ltd. www.els.net
Secondary article
. Introduction
Article Contents
. Opening or Closing of an Ion Channel: the Most Rapid
Transduction Mechanism
. Production of Either an Excitatory or Inhibitory
Postsynaptic Potential by Directly Coupled Receptor/
Ion Channel Systems
. Initiation of Biochemical Events by Metabotropic
Receptor Activation
. Calcium Ions as a Major Intracellular Second
Messenger
. Increase in Levels of Intracellular Calcium by Activation
of Both Directly Coupled Ion Channel Receptor
Systems and Metabotropic Receptors
. Cyclic Nucleotides as Second Messengers
. Regulation by Metabotropic Receptors of the Enzyme
that Synthesizes Cyclic AMP
. Regulation of Certain Ion Channels by Calcium and
Cyclic Nucleotides
. Transfer of Phosphate onto other Proteins by Protein
Kinases: Modulation of Function
. Calcium and Cyclic Nucleotide-regulated Protein
Kinases
. Summary
gated ion channels allows passage of ions through the
receptor itself (Figure 1).
Opening or Closing of an Ion Channel:
the Most Rapid Transduction
Mechanism
The resting membrane potential of excitable cells, nerve
cells and muscle cells, exists due to the difference between
the intracellular concentrations of the ions chloride,
sodium, potassium and calcium and the extracellular
concentrations of these ions. The concentration differences
alone cause a concentration gradient across the membrane,
while the separation of charge across the membrane causes
an electrical gradient. This electrochemical gradient
provides the energy necessary to drive ions across the
membrane rapidly, causing action potentials, muscle
contractions or intracellular signalling events, depending
on the cell type.
Proteins spanning the membrane allow the passage of
specific ions or specific combinations of ions in response to
various cellular signals including changes in the membrane
potential (voltage-gated ion channels) and chemical signals
(ligand-gated ion channels and cyclic nucleotide-gated
channels). Opening and closing, or gating, of these
1
 Receptor Transduction Mechanisms
channels happens rapidly, allowing for changes in mem-
brane potential and calcium concentration, which, as we
will discuss in more detail, is an important signal for
various cell processes. Since ligand binding is the single
event required to permit the passage of ions to initiate an
action potential or muscle contraction, this signal trans-
duction occurs more rapidly than the signals for other cell
functions.
Production of Either an Excitatory or
Inhibitory Postsynaptic Potential by
Directly Coupled Receptor/Ion Channel
Systems
A neurotransmitter is often classified as excitatory or
inhibitory based on its action to either promote or inhibit
the generation of an action potential in an excitable target
cell. Stimulation of an excitatory neurotransmitter recep-
tor generally increases the permeability of the membrane to
sodium or calcium, thereby depolarizing the cell and
making an action potential more likely. The resulting
depolarization is called an excitatory postsynaptic poten-
tial or EPSP. In contrast, stimulation of an inhibitory
neurotransmitter receptor generally increases the mem-
brane’s permeability to potassium or chloride, thereby
hyperpolarizing the cell and decreasing the likelihood of an
action potential. This hyperpolarization is known as an
inhibitory postsynaptic potential or IPSP. Table 1 contains
a list of common neurotransmitters and the selectivity of
the channels that they open.
Binding of a neurotransmitter to a ligand-gated ion
channel causes a conformational change in the channel,
Table 1 List of common neurotransmitters and their properties
Neurotransmitter Ionotropic receptor Channel permeability
Glutamate NMDA, AMPA, kainate Cations, Na+ >> Ca2+
Acetylcholine Nicotinic Cations
GABA GABAA Anions
Glycine Glycine Anions
NMDA, N-methyl-D-aspartate; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxalone propionic acid; GABA, γ-aminobutyric acid; EPSP, excitatory
postsynaptic potential; IPSP, inhibitory postsynaptic potential.
2
allowing particular ions to pass through the channel. Since
the ion channel is actually the receptor for the ligand, this
change in permeability occurs on the order of milliseconds.
Synapses containing these types of ion channels are often
called fast synapses, and can be excitatory or inhibitory.
Nicotinic acetylcholine receptors and glutamate receptors
are excitatory ligand-gated channels, while GABA (g-
aminobutyric acid) and glycine are inhibitory ligand-gated
channels.
The nicotinic acetylcholine receptor (nAChR) has been
studied extensively at the neuromuscular junction and in
autonomic ganglia. When acetylcholine is released from
nerve terminals at the neuromuscular junction, it binds to
its ionotropic receptor which undergoes a conformational
change. Ionotropic receptors are ligand-gated channels
which means that upon agonist binding, the receptors
(which are themselves channels) open. This allows the
passage of cations, mainly sodium in the case of the
nAChR, into the cell, depolarizing the cell. The voltage
change opens voltage-gated calcium channels and the
influxing calcium binds to the contractile proteins in the
muscle cell, causing a contraction. Acetylcholine also
activates a second type of receptor, the muscarinic
acetylcholine receptor (mAChR). Because activation of
this receptor does not directly alter membrane perme-
ability, it is referred to as a metabotropic receptor.
Historically, the term metabotropic has been used to
distinguish effects of neurotransmitters acting through
cascade mechanisms from the effects of the same neuro-
transmitter to directly gate channels. For the purposes of
discussion in this article, we will refer to any receptor that
signals through second messengers as a metabotropic
receptor. Receptors of this type will be considered in other
sections of this article.
Effect on membrane
potential Cellular consequence
Depolarizing EPSP
Depolarizing Muscle contraction, EPSP
Hyperpolarizing IPSP
Hyperpolarizing IPSP

When glutamate binds to its receptor on a neuron, the
receptor channels open and allow sodium and calcium to
pass into the cell, depolarizing the cell. If enough channels
open, the cell will depolarize to threshold, the membrane
potential at which the neuron fires an action potential. The
depolarization will be conducted down the axon of the
neuron to the nerve terminal causing calcium influx and
neurotransmitter release. Thus the glutamate signal is
passed from the original target neuron to another cell. Like
acetylcholine, glutamate has more than one receptor type.
The types of ionotropic receptors activated by glutamate
are distinguished based on their affinity for glutamate
structural analogues. Agonist N-methyl-d-aspartate
(NMDA) binds with high affinity to NMDA receptors,
while the non-NMDA receptors are named for their high-
affinity agonists a-amino-3-hydroxy-5-methyl-4-isoxalone
propionic acid (AMPA) and kainate. Additionally, gluta-
mate can activate metabotropic receptors (mGluR) which
have important actions on neuronal function.
The binding of the inhibitory neurotransmitter GABA
to the GABAA receptor produces a rapid and transient
increase in membrane permeability to chloride ions. This
increased chloride current hyperpolarizes the cell, pushing
the resting membrane potential farther from threshold and
decreasing the likelihood of an action potential. Like
acetylcholine and glutamate, GABA also activates a
metabotropic receptor, GABAB.
Initiation of Biochemical Events by
Metabotropic Receptor Activation
Metabotropic receptors require second messengers to
convey their signal inside the cell and stimulation results
in cellular changes on the order of seconds or minutes. Such
receptors reside in the plasma membrane and do not form a
hydrophilic pore. Instead, they act to transduce a signal
between the extracellular milieu and the cytoplasm.
Specific binding of an agonist causes activation of the
receptor that spans the membrane. The resulting con-
formational change is translated into a signal on the
intracellular surface of the membrane. Some receptors,
such as receptor tyrosine kinases and receptor guanylyl
cyclases, have intrinsic enzymatic activity that is activated
when agonist binds. Other receptors are coupled to signal
transduction proteins that may have catalytic activity or
may themselves activate other enzymes. In any case, the net
effect is a signal that crosses the membrane. Since
activation of transmembrane receptors causes a down-
stream effect, this opens the possibility of amplification of
the signal. Stimulation of a membrane receptor can
produce many active second messengers which may then
affect several target proteins, thus amplifying the signal.
Various neurotransmitter and hormone receptors are G
protein-coupled. High-affinity binding of the neurotrans-
Receptor Transduction Mechanisms
mitter to the receptor causes a change in the receptor which
allows the associated G protein a subunit to dissociate
from the b and g subunits and exchange guanosine
diphosphate (GDP) for guanosine triphosphate (GTP).
The active GTP-bound form of the Ga subunit can then
stimulate or inhibit various enzymes, depending on the
particular type of subunit that typically associates with a
certain receptor. Additionally, it has recently become
accepted that the bg subunits act in concert and also
stimulate or inhibit cellular functions.
Unlike ionotropic receptors which produce responses
lasting for milliseconds, metabotropic receptors can
produce cellular responses that may last for seconds. In
the case of metabotropic GABA and glutamate receptors,
the receptors are G protein coupled to varied effector
mechanisms. Through metabotropic receptors, neuro-
transmitters can not only be excitatory or inhibitory, but
can also influence a number of other cellular functions. The
GABAB receptor, for example, is coupled to two G protein
types: Gi and Go. The mGluR is coupled to various signal
transduction systems in different brain regions, depending
on cell type. Through these transduction pathways, the
metabotropic receptors can modulate cell functions like
second messenger cascades, protein kinase activity and ion
channel activity.
Calcium Ions as a Major Intracellular
Second Messenger
Small changes in intracellular calcium concentration can
have profound effects on the cell. The normal resting
calcium concentration in a living cell is on the order of
100 nmol L 2 1. Cells maintain this low concentration by
actively pumping calcium out of the cell or into organelles
like the mitochondria, the sarcoplasmic reticulum or the
endoplasmic reticulum.
Some of the actions of calcium as a signal molecule
require calmodulin. Calmodulin is ubiquitously expressed
in all cell types, both as an independent molecule or as a
component of an enzymatic complex. The binding of
calcium to calmodulin causes a conformational change
that activates or inhibits target proteins which may
themselves go on to catalyse reactions. For example, when
intracellular calcium concentrations are sufficiently high,
calcium binds to free calmodulin molecules. This complex
can then interact with and activate the calcium ATPase on
the sarcoplasmic reticulum that pumps calcium into the
organelle. In this way, the cell senses that the intracellular
calcium levels are high and quickly sequesters the ions.
Muscle cells require an increase in intracellular calcium
to contract. The calcium ions bind to various contractile
proteins and other enzymes which then go on to catalyse
downstream reactions. In neurons, chemical synapses
require calcium for the release of neurotransmitter from
3
 Receptor Transduction Mechanisms

the presynaptic nerve terminal. Influx of calcium is

necessary for the vesicles to fuse with the plasma 1. Ligand binds to G protein-
coupled receptor, coupled
membrane and release the neurotransmitter. Other secre- to Gαq
tory cells that secrete via vesicular release also depend on
an increase in calcium current. Intracellular calcium ions αq βγ
Ca2+
can also modulate gating of ion channels. Calcium ions can Ca2+
2. Gαq exchanges
Ca2+
increase the permeability of a certain class of potassium GTP
GDP GDP for GTP
channels and a type of chloride channel. The voltage-gated Ca2+
calcium channels themselves are modulated by intracel- VDCC
Ca2+ 3. Gαq stimulates
lular calcium. phospholipase to αq
+++ catalyse conversion
of PIP2 to DAG +
PIP2
IP3
DAG + IP3
Increase in Levels of Intracellular PKC 2+
Ca
Calcium by Activation of Both Directly 4. DAG stimulates PKC to Ca2+
Ca2+

Coupled Ion Channel Receptor Systems increase Ca2+ influx through

VDCCs while IP3 binds to its
Ca2+ Ca2+
2+
Ca2+ Ca2+ 2+ Ca
and Metabotropic Receptors receptor on the SR or ER and Ca

liberates intracellular Ca2+ stores

Because changes in calcium concentration are so crucial to
many cellular processes, cells have many mechanisms by
which calcium ions can enter the cytoplasm. Changes in
membrane potential, as in an action potential, can cause
the opening of voltage-dependent calcium channels.
Calcium ions flow through the channels from the extra-
cellular space. Agonist binding to some ligand-gated
channels, such as the nicotinic acetylcholine receptors
and the NMDA receptors, allows the passage of ions
including calcium into the cell through the receptor itself.
Agonist binding to nonchannel receptors requires second
messengers to change the calcium concentration in the cell.
Activation of mGluR in some cell types causes Gaq to
exchange GDP for GTP. Gaq then activates a phospho-
lipase which catalyses the conversion of phosphoinositol
4,5-bisphosphate (PIP2) to inositol 1,4,5-trisphosphate
(IP3) and diacylglycerol (DAG). Excitable cells store
calcium in specialized organelles called the endoplasmic
reticulum (ER) or the sarcoplasmic reticulum (SR). The
ER or SR sequester calcium from the cytosol by means of a
calcium ATPase. These organelles have receptors for the
signal molecule IP3 which is formed by stimulation of Gaq-
coupled receptors. Binding of IP3 to its receptor liberates
calcium from these stores. DAG, along with calcium,
activates protein kinase C (PKC), a protein which adds a
phosphate group to other proteins, altering their activity.
Studies have shown that PKC can phosphorylate voltage-
gated calcium channels, allowing them to pass more
calcium when they open. Thus mGluR activation causes
an increase in intracellular calcium in a biphasic manner,
both releasing intracellular calcium and increasing the
membrane permeability to calcium (Figure 2).
Other G protein cascades can also increase intracellular
calcium concentrations by altering voltage-gated channels.
b-Adrenergic receptor stimulation, for example, causes an
increase in intracellular cAMP levels, which activates a
kinase known as protein kinase A (PKA). This kinase has
Figure 2 Generalized Gq-coupled receptor pathway causing an increase
in intracellular calcium concentration. PIP2, phosphoinositol 4,5-
bisphosphate; IP3, inositol 1,4,5-trisphosphate; DAG, diacylglycerol; PKC,
protein kinase C; VDCC, voltage-dependent calcium channel; SR,
sarcoplasmic reticulum; ER, endoplasmic reticulum; GDP, guanosine
diphosphate; GTP, guanosine triphosphate.
been shown to increase voltage-dependent calcium influx
in the heart, skeletal and smooth muscle.
Cyclic Nucleotides as Second
Messengers
Because cyclase enzymes are activated secondary to the
binding of the ligand to the receptor, cAMP and cGMP are
referred to as second messengers. Just as the level of
intracellular calcium ions effects many cellular processes,
the level of cyclic nucleotides can regulate many enzymatic
actions and channel activity. Cyclic nucleotides can act as
messengers by activating protein kinases which then go on
to phosphorylate many types of proteins in the cell and
alter their activity. Additionally, cAMP and cGMP can
interact with target proteins directly to modify their
function. Through these two mechanisms, cyclic nucleo-
tides, like calcium, can act via direct or indirect methods.
Regulation by Metabotropic Receptors
of the Enzyme that Synthesizes Cyclic
AMP
The signal that a particular ligand passes onto a cell
depends on the type of receptor for that ligand present on

4
 Receptor Transduction Mechanisms

the target cell as well as on the signal transduction Regulation of Certain Ion Channels by
molecules coupled to that receptor in that particular cell
type. Since most cells contain thousands of types of
Calcium and Cyclic Nucleotides
receptors, there is a dynamic regulation of the intracellular
Membrane depolarizations can cause an increase in
signalling, and the signals often overlap or oppose each
intracellular calcium concentration as described above.
other.
During an action potential, for example, calcium enters the
The level of cAMP in a cell is dynamically regulated by
cell during the depolarizing phase. To terminate the action
opposing G protein actions (Figure 3). Adenylate cyclase
potential, several types of potassium channels are activated
catalyses the conversion of ATP to cAMP. Gas stimulates
to extrude potassium and return the cell to its hyperpolar-
the adenylate cyclase enzyme, while Gai inhibits it.
ized resting membrane potential. One of these channels is
Adrenaline binds to b-adrenergic receptors on muscle cells
the calcium-activated potassium channel. There are two
and the resulting signal cascade brings about glycogen-
subtypes of this channel, the big K 1 (BK 1 ) and the small
olysis and changes in membrane permeability. Stimulation
K 1 (SK 1 ). They are named for their conductances of
of the receptor liberates a Gas subunit which in turn
greater than 100 pS and less than 80 pS, respectively
stimulates production of cAMP via adenylate cyclase. As
(reviewed in Latorre et al., 1989).
mentioned previously, PKA phosphorylation of calcium
Many nonexcitable cells as well as cells that have action
channels can cause increased voltage-dependent calcium
potentials express channels that are activated by binding of
influx, and such an increase in calcium current is observed
cyclic nucleotides (cAMP and cGMP). These channels are
upon adrenaline stimulation of the heart. The increased
nonspecific cation channels which permit the flow of
intracellular calcium results in the quickening of the
sodium, potassium or calcium. Sensory cells make use of
heartbeat and increased force of contraction associated
the cyclic nucleotide-gated nonspecific channels. Photo-
with adrenaline.
transduction for example, requires cGMP-gated channels.
Vagus nerve terminals providing sympathetic innerva-
In rods and cones, cGMP is at relatively high concentra-
tion to the heart release acetylcholine. The cardiac muscle
tion until light stimuli activate phosphodiesterases that
expresses muscarinic acetylcholine receptors (mAChR)
convert cGMP back to 5’-GMP. cGMP-gated channels
which are G protein coupled. The receptor is linked to both
close under these conditions, preventing the secretion of
Gi and Gq so it inhibits adenylate cyclase and activates the
glutamate onto the bipolar cells of the retina. In olfaction,
phospholipase cascade. The Gi inhibits the cAMP produc-
a specialized G protein, Golf, is stimulated to exchange
tion thus reducing the activity of PKA and therefore the
GDP for GTP when the receptor is stimulated by an
increase in calcium influx associated with the adrenaline
odorant molecule. The activated Golf then stimulates
stimulation. Additionally, stimulation of mAChR is
adenylate cyclase to produce cAMP which in turn opens
associated with enhanced inwardly rectifying potassium
a cation channel.
current. Interestingly, the bg subunits have been shown to
Additionally, calcium can activate chloride channels.
interact directly with the associated potassium channel
The physiological relevance of the calcium-activated
(KAch). Due to the presence of both mACh receptors and
chloride channel is unclear, but it probably serves to
adrenaline receptors on cardiac muscle, the contractile
stabilize the resting membrane potential, since chloride is
force and rate of the heart can be dynamically controlled.
passively distributed across the membrane. In vascular
smooth muscle, this channel causes membrane depolariza-
tion upon activation by an agonist.

β–Ad mAChR
βγ αs αi βγ
K+
K+ K+
K+
Ca2+ ++ ––
Ca2+ ++ KAch
2+
Ca2+ Ca
2+
Adenylyl +
Ca Ca2+ K
cyclase K+
Ca2+ K+
VDCC ++
cAMP
PKA

Figure 3 Crosstalk between receptor transduction pathways allows for dynamic regulation of cellular processes. b-Ad, b-adrenergic receptor; mAChR,
muscarinic acetylcholine receptor; PKA, protein kinase A; VDCC, voltage-dependent calcium channel; KAch, potassium channel; cAMP, cyclic adenosine
monophosphate.

5
 Receptor Transduction Mechanisms
Transfer of Phosphate onto other
Proteins by Protein Kinases: Modulation
of Function
Protein phosphorylation is well documented as a major
mechanism for altering the activity of enzymes and channel
proteins. The terminal phosphate of ATP is transferred
and covalently bound to a hydroxyl group of the target
protein by a kinase. Two major groups of kinases are
known: tyrosine kinases and serine/threonine kinases.
These groups are named for the residue they typically
phosphorylate on a target protein. A phosphorylation
event can be stimulatory or inhibitory, depending on the
target protein and the phosphorylation site.
The ultimate effect of many signal transduction cascades
is to alter the phosphorylation state of target proteins.
Phosphorylation events have been linked to alterations in
membrane permeability, activation of gene transcription,
modification of enzyme activity and more. The substrates
for phosphorylation vary from cell type to cell type and the
substrates present will determine the ultimate effect of the
kinase.
Calcium and Cyclic Nucleotide-
regulated Protein Kinases
As mentioned earlier, DAG activates PKC isozymes which
are serine/threonine kinases. Some isoforms of PKC also
require an increase in intracellular calcium to be fully
active. A large number of proteins have been shown to be
phosphorylated by PKC, both in vitro and in vivo. Proteins
containing the PKC consensus phosphorylation motif are
likely targets for regulation by signal cascades activating
PKC. There are subtle differences in the motifs preferred by
different PKC isozymes, but all require basic residues
surrounding the threonine or serine (Nishikawa et al.,
1997). In the brain, PKC activation has been shown to alter
ionic currents. The effects of PKC on specific ionic
currents, whether stimulatory or inhibitory, are not easily
generalized and depend on the presence of channel
accessory subunits and the colocalization of the compo-
nents of the signal cascade.
PKA is the primary effector of cAMP. Another serine/
threonine kinase, PKA, phosphorylates residues that are
flanked on their N-terminal side by two or more basic
amino acids. PKA is thought to account for all of the effects
of cAMP except for those in some central neurons
including olfactory neurons, where cAMP gates an ion
channel directly. cAMP-dependent phosphorylation was
first demonstrated in skeletal muscle cells. Adrenaline
stimulates the b-adrenergic receptor in these cells and the
resulting metabolic cascade involves PKA. The increase in
cAMP concentration in the cell promotes activity of PKA
6
which phosphorylates glycogen synthase, reducing the
activity of the enzyme and thus reducing storage of glucose
as glycogen. Additionally, PKA adds a phosphate group to
glycogen phosphorylase kinase which then phosphorylates
glycogen phosphorylase. The activation of this enzyme by
addition of a phosphate catalyses the release of glucose
from glycogen stores. PKA can also work directly by
altering ion channels through phosphorylation of the
channel proteins, as mentioned for the calcium channels in
cardiac cells.
cGMP binds to protein kinase G (PKG) which can then
phosphorylate a number of target proteins. The atrium of
the heart, under conditions of increased blood pressure,
releases atrial natriuretic peptide (ANP). ANP stimulates
sodium secretion from the kidney and relaxation of the
vasculature, both effects which lower blood pressure. The
receptor for ANP is a transmembrane receptor with an
intracellular guanylyl cyclase domain. Binding of ANP
activates the cyclase which converts GTP to cGMP which
then activates PKG. Substrates for PKG include ion
channels such as voltage-dependent calcium channels as
well as cytoskeletal elements and nitric oxide synthase.
Like PKC and PKA, PKG is a serine/threonine kinase.
Few substrates of PKG are exclusively phosphorylated by
PKG (reviewed in Wang and Robinson, 1997). There is an
overlap with PKA specificity, so a specific phosphorylation
motif is unclear.
Important mediators of calcium activity in cells are the
calcium/calmodulin-dependent protein kinases (CaM ki-
nases). Some of these kinases, like myosin light-chain
kinase which provokes smooth muscle cell contraction,
have very specific substrates. Others, like CaM kinase II,
are utilitarian in that their specific actions are determined
by which substrates are present in the cell.
Summary
Peptide signals which cannot cross the membrane are
received and transmitted to the intracellular space via two
mechanisms: direct opening of ion channels or production
of a receptor-mediated signal cascade. The actions of
agents which open the ligand-gated ion channels are
immediate because the receptor itself allows passage of
ions into or out of the cell. Ligands that stimulate
metabotropic receptors, however, signal through activa-
tion of intracellular proteins which produce second
messengers. Increases in intracellular calcium, cAMP and
cGMP are important catalysts for intracellular processes
both directly and through activation of kinases.
The effect a particular signal has on a target cell depends
on the other active signals as well as the signal transduction
processes and substrates expressed in that particular cell
type. Many of these pathways interact with or oppose each
other. Such crosstalk allows for finely tuned dynamic

regulation of cellular processes and integration of the many
signals a cell receives from its environment.
References
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calcium-activated potassium channels. Annual Review of Physiology.
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protein kinase C isozymes. Journal of Biological Chemistry 272: 952–
960.
Wang X and Robinson PJ (1997) Cyclic GMP-dependent protein kinase
and cellular signalling in the nervous system. Journal of Neurochem-
istry 68: 443–456.
Further Reading
Alberts B, Bray D, Lewis J, Raff M, Roberts K and Watson J (1994)
Molecular Biology of the Cell, 3rd edn. New York: Garland Publish-
ing.
Receptor Transduction Mechanisms
Gilman AG (1987) G proteins: transducers of receptor-generated
signals. Annual Review of Biochemistry 56: 615–649.
Hammond C (ed.) (1996) Cellular and Molecular Neurobiology. New
York: Academic Press.
Hille B (1992) Ionic Channels of Excitable Membranes, 2nd edn.
Sunderland, MA: Sinauer Associates.
Neer EJ and Clapham DE (1988) Roles of G protein subunits in
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Nicoll RA (1988) The coupling of neurotransmitter receptors to ion
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Nicoll RA, Malenka RC and Kauer JA (1990) Functional comparison of
neurotransmitter receptor subtypes in mammalian central nervous
system. Physiological Reviews 70: 513–565.
Ross EM (1989) Signal sorting and amplification through G protein-
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Sleight RG and Lieberman MA (1998) Signal transduction. In:
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