CELL
COMMUNICATION
CAMPBELL & REECE
CHAPTER 11
Cell Messaging
 some universal mechanisms of
cellular regulation
 cells most often communicate with
other cells by chemical signals
Evolution of Cell Signaling
 Yeast: Saccharomyces cerevisia
 2 sexes: a & α
 type a secrete a signaling molecule called “a
factor” which can bind to receptor proteins
on α cells
 @ same time α cells secrete “α factor” which
binds to receptor proteins on type a cells
Saccharomyces cerevisiae
 2 mating factors then cause the 2 yeast cells
to grow toward each other & initiate other
cell changes
 results in fusion or mating of 2 cells of
opposite type  a/α cell that contains genes
of both original cells
 this new cell later divides passing this
genetic combination to their offspring
Signal Transduction Pathway
 series of steps initiated by signal molecule
attaching to receptor
 mechanism similar in yeasts and mammals
& between bacteria and plants
 Scientists think signaling mechanisms 1st
evolved in ancient prokaryotes & unicellular
eukaryotes then adopted for new uses by
their multicellular descendants
Communication Among Bacteria
 quorum sensing: bacteria release small
molecules detected by like bacteria: gives
them a “sense” of local density of cells
 allows them to coordinate activities only
productive when performed by given # in
synchrony
 ex: forming a biofilm: aggregation of bacteria
adhered to a surface: slime on fallen leaves
or on your teeth in the morning (they cause
cavities)
Biofilm Developing
Biofilm Development
Local Signaling
 (eukaryotic cells can also use cell junctions)
 secretion of chemicals = messenger
molecules from signaling cell
 messenger molecules that travel to nearby
cells only called: local regulators
Local Regulators
 Animals: use 1 class of local regulators:
 growth factors
 many cells in neighborhood respond to
growth factor produced by 1 cell
 paracrine signaling: secreting cell acts on
nearby target cells by discharging local
regulator
Paracrine Signaling
Synaptic Signaling
 in the animal nervous system
 action potential travels thru cell membrane
of neuron  when the electrical signal
reaches axon end it triggers exocytosis of
neurotransmitter (messenger molecule)
 neurotransmitter travels across small space
(synapse)  attaches to receptors on target
cell
Synaptic Signaling
Local Signaling in Plants
 not as well understood as in animals
 use hormones (as do animals): long distance
signaling aka endocrine signaling
 travel  target cells (any cell that has
receptor for hormone)
 Plant hormones aka plant growth regulators
 most reach their targets by moving cell-tocell
 some travel in vessels
Long Distance Signaling
 hormones (in some cases)
 neurotransmitters: electrical signal travels
length of neuron, may go from neuron-toneuron for long distances
 ability for any cell to respond to messenger
molecule requires cell to have receptor for
that particular molecule
3 Stages of Cell Signaling
1. Reception
target cell’s detection of the signal
2. Transduction
 receptor protein changes converting
signal to a form that can bring about
specific cellular response via a signal
transduction pathway
3. Response
 activation of cellular response

Stages of Cell Signaling Response
Reception
 cells must have a receptor for the ligand
(messenger molecule) to react with
 many signal receptors are transmembrane
proteins with water-soluble ligands
ligands:
usually large
hydrophilic
Membrane Receptors
G-Protein-Coupled Receptors
 cell-surface transmembrane receptor
 works with help of a G protein (protein that
binds to GTP)
 flexible
 inherently unstable

difficult to crystallize so can study structure (use
x-ray crystallography)
G Protein-Coupled Receptor: 7 α helices
Receptor Tyrosine Kinases
 major class of membrane receptors
w/enzyme activity
 kinase: enzyme that catalyzes addition of
phosphate group
 cytoplasmic side of receptor has enzyme that:
phosphate group from ATP  tyrosine (on
substrate protein)
Tyrosine
Inactive Monomers of Tyrosine Kinase
 When there is no
ligand attached to
receptor site the
kinase receptor
protein exists as
monomers
Binding of Signaling Molecule: Form Dimers
Tyrosine Kinase Activated by Dimerization
 phosphate group
added to each
tyrosine
Recognition by Relay Proteins
 Relay proteins
attach to
phosphorylated
tyrosine 
structural change
that activates the
bound protein
 Each activated
relay protein
triggers different
transduction
pathway  specific
cellular response
ION CHANNEL RECEPTORS
 Ligand-Gated Ion Channels
Ligand Binds to Receptor Site
 ion crosses
membrane &
enters
cytoplasm 
transduction
pathway leading
to a response
Ligand Dissociates from Receptor Site
Intracellular Receptors
 in cytoplasm or nucleus of target cells
 hydrophobic or very small ligands
 examples
 steroid hormones & thyroid hormones of
animals
 NO (nitric oxide), a gas
Turning on Genes
 special proteins called transcription factors
control which genes are turned on
 example:
 Testosterone (steroid hormone)
 its activated receptor acts as transcription
factor that turns on specific genes
 thus activated receptor carries out
transduction of the signal
TRANSDUCTION
 when receptors for signaling molecules are
membrane proteins the transduction stage is
multistep pathway
 usually involves inactive/active state by
adding/removing phosphate group
 benefit of multistep pathway is that
possibility of amplification of signal

if each step on pathway can transmit signal to
several molecules end up with large # activated
molecules @ end of pathway
Signal Transduction Pathway
 in most cases original signaling molecule
does not enter cell & is not passed along
signaling pathway
 1st step triggered by signaling molecule
binding to receptor
 proteins often used as relay molecules
(protein interaction a unifying theme of all
cellular regulation)
Protein Phosphorylation & Dephosphorylation
 protein kinase: enzyme that transfers
phosphate groups from ATP  protein
 most act on proteins different than
themselves
 most act on a.a. serine or threonine (not
tyrosine as in previous example)
 includes kinases in plants, animals, &
fungi
 many relay molecules in pathway are
kinases
Phosphorylation Cascade
Protein Phosphatases
 enzymes that can rapidly remove phosphate
groups from proteins (inactivating them)
 also make kinases available to reuse
 this phosphorylation/dephosphorylation
system acts as molecular “switch” in cell
“position of the switch” @ any given time
depends on balance between active kinase &
active phosphatase molecules
Second Messengers
 many signaling pathways involve small,
nonprotein, water-soluble molecules or ions
known as 2nd messengers
 1st messenger is extracellular signaling
molecule
 2 most widely used 2nd messengers are cAMP
& Ca++
Cyclic AMP
 epinephrine causes glycogen in hepatocytes
to  glucose w/out entering cells
 search for 2nd messenger that transmits
signal from plasma membrane  metabolic
pathway in cytoplasm
 epinephrine binding to receptor followed by
elevation of cytosolic concentrations of
cAMP
cAMP
ATP
cAMP
Adenylyl Cyclase
 enzyme embedded in plasma membrane
 ATP  cAMP in response to extracellular
signals directly or indirectly(epinephrine one
of many)
 indirectly: receptor protein changes when
signaling molecule attaches  activates many
adenylyl cyclase possibly thru GTP
GTP
cAMP as 2nd
Messenger
1st messenger
activates G
protein-coupled receptor 
adenylyl
cyclase  ATP
to cAMP 
activates
another
protein
(usually
protein kinase
A)
Protein Kinase A
 serine/threonine kinase
 once activated it will phosphorylate other
proteins (depends on cell type)
Other Regulation Mechanisms
 G protein systems inhibit adenylyl cyclase
 uses different signaling molecule & receptor
 understanding role of cAMP helps to explain how
certain microbes cause disease
 Vibrio cholerae: causes cholera
 in contaminated water
 forms biofilm over small intestines
 produces a toxin: enzyme that chemically
modifies a G protein involved in regulation
of water & salt secretion (GTP --/ GDP so
protein stays stuck in active form)  high
[cAMP]  cells secrete large amts salts 
followed by water (osmosis)
Vibrio cholerae
Calcium Ions
 many signaling molecules induce responses
in target cell using signal transduction
pathways that increase intracellular [Ca++]
 more widely used than cAMP as 2nd
messenger
Effects of Ca++
Animal Cells
 contraction
 secretion
 cell division
Plant Cells
 pathway that leads
to greening in
response to light
Ca++ Concentration Gradient
 normally, [Ca++] inside cell << than outside
 (up to 10,000x higher in extracellular fluid)
 pumps used to send Ca++ into SER in muscle
fibers (also in mitochondria, chloroplasts)
 pathway leading to release of Ca++ from SER
involves the 2nd messengers:
1. IP3 (inositol triphosphate)
2. DAG (diacylglycerol)
Ca++ Pathway in Tear Production
RESPONSE
 can be either nuclear or cytoplasmic
responses
 in nuclear responses the last kinase enters
nucleus  activates gene-regulating protein
aka a transcription factor  gene(s)
transcribed  mRNA …..
 or transcription factor can turn gene off
 Transcription factors can regulate several
different genes
Nuclear Response thru signal reception 
transduction (phosphorylation cascade) 
gene activation
Cytoplasmic Response
 signaling pathway may regulate activity of a
pathway (not synthesis of a protein)
 open/close ion channel
 change cell metabolism by controlling
enzymes
 regulate cell activities (yeast build
projections toward cell of opposite mating
type)
Yeast Reproduction
How do signals induce directional cell
growth during mating in yeast?
1. mating factor activates receptor
2. G protein binds GTP & becomes activated
3. phosphorylation cascade activates Fus3
which then moves to plasma membrane
4. Fus3 (a kinase) phosphorylates formin this
activating it
5. formin initiates growth of microfilamentsw
that form shmoo projections
Controlling Response
 generally, response controlled @ >1 site (not
just either “on” or “off”)
 4 aspects of fine-tuning response:
1. Signal amplification
2. Specificity
3. Efficiency
4. Termination of signal
Signal Amplification
 enzyme cascades amplify the cell’s response
to a signal
 @ each step the # of activated products much
> in preceding step of cascade
 amplification happens because activated
protein kinase stays in activated form long
enuf to process numerous molecules of
substrate
 as result a small # signal molecules (like
epinephrine) can release 100’s of millions of
final product (glucose molecules)
Specificity of Cell Signaling &
Coordination of the Response
 certain cells respond to some signals & have
no response to others
 2 different cells may have different responses
to same signal
 different kinds of cells turn on different
genes so different kinds of cells have
different collections of proteins
What controls responses in cells?
 response of a particular cell to a signal
depends on its particular collection o
1. signal receptor proteins
2. relay proteins
3. proteins necessary to carry out the response
Signaling Efficiency: Scaffolding Proteins
& Signaling Complexes
 Scaffolding Proteins: type of large relay
protein to which several other relay proteins
are simultaneously attached increasing the
efficiency of signal transduction
Scaffolding Proteins Respond to same
Signal
Scaffolding Proteins
 some are permanently held together
(terminal axons in neurons)
Relay Proteins that are Branch Points
 Wiskott-Aldrich
Syndrome (WAS)
defect in single relay
protein leads to:
 abnl bleeding
 eczema
 predisposition to:
 infections
 leukemia
Termination of the Signal
 ability of cell to respond to new signals
depends on reversibility of changes produced
by prior signals
 binding of signal molecules to receptors is
reversible
as [signal molecules] decreases fewer receptor
sites occupied by signal
 those unoccupied: receptor molecule reverts to
its inactive form

Termination of Signal
 any particular cell response occurs only
when concentration of occupied receptors
has reached a certain threshold:
 if below threshold the cell response stops
relay molecules return to inactive form
 cAMP  AMP
 phosphorylated kinases lose phosphate group

Apoptosis integrates multiple cellsignaling pathways
 apoptosis: programmed cell death
 Steps:
1. DNA gets copped up into pieces
2. organelles & other cytoplasmic components
fragment
3. cell‘s parts put into vesicles which are
engulfed by phagocyctic cells
4. “blebbing” occurs (cell becomes multilobed)
Apoptosis in Soil Worm C. elegans
 2 genes identified Ced4 & Ced3 (ced for cell
death)
 both encode for proteins essential for cell
death
 are always present in a cell in inactive form
 C. elegans has protein in outer mitochondrial
membrane called Ced9 (from gene of same
name) which serves as master regulator of
apoptosis (has its brake on until “death
signal” overrides it)
Signals that Trigger Apoptotic Pathways
 capase: group of proteins that mediate
apoptosis
 several different pathways involving 15
capases identified in mammals
 which pathway used depends on type of cell &
signal used
 1 major pathway involves mitochondrial
proteins that form pores in mitochondrial
membrane releasing mitochondrial proteins,
including cytochrome c,  activate capases