Overview: Cellular Messaging

• Cell-to-cell communication is essential for both

multicellular and unicellular organisms
• Biologists have discovered some universal
mechanisms of cellular regulation
• Cells most often communicate with each other
via chemical signals
 Evolution of Cell Signaling
• The yeast, Saccharomyces cerevisiae, have
two mating types, a and 
• Cells of different mating types locate each
other via secreted factors specific to each type
• A signal transduction pathway is a series of
steps by which a signal on a cell’s surface is
converted into a specific cellular response
• Signal transduction pathways convert signals
on a cell’s surface into cellular responses
Figure 11.2
 factor
Receptor
1 Exchange
of mating
factors a 

a factor
Yeast cell, Yeast cell,
mating type a mating type 

2 Mating

a 

3 New a/ cell

a/
• Pathway similarities suggest that ancestral
signaling molecules evolved in prokaryotes and
were modified later in eukaryotes
• The concentration of signaling molecules allows
bacteria to sense local population density
 Local and Long-Distance Signaling
• Cells in a multicellular organism communicate
by chemical messengers
• Animal and plant cells have cell junctions that
directly connect the cytoplasm of adjacent cells
• In local signaling, animal cells may communicate
by direct contact, or cell-cell recognition
Figure 11.4
Plasma membranes

Gap junctions Plasmodesmata

between animal cells between plant cells
(a) Cell junctions

(b) Cell-cell recognition

• In many other cases, animal cells communicate
using local regulators, messenger molecules
that travel only short distances
• In long-distance signaling, plants and animals
use chemicals called hormones
• The ability of a cell to respond to a signal
depends on whether or not it has a receptor
specific to that signal
 Figure 11.5a

Local signaling

Target cell Electrical signal

along nerve cell
triggers release of
neurotransmitter.

Neurotransmitter
Secreting Secretory diffuses across
cell vesicle synapse.

Local regulator
diffuses through Target cell
extracellular fluid. is stimulated.

(a) Paracrine signaling (b) Synaptic signaling

Figure 11.5b
Long-distance signaling

Endocrine cell
Blood
vessel

Hormone travels
in bloodstream.

Target cell
specifically
binds
hormone.

(c) Endocrine (hormonal) signaling

 The Three Stages of Cell Signaling:
A Preview
• Earl W. Sutherland discovered how the
hormone epinephrine acts on cells
• Sutherland suggested that cells receiving signals
went through three processes
– Reception
– Transduction
– Response
 Figure 11.6-3

EXTRACELLULAR CYTOPLASM
FLUID Plasma membrane

1 Reception 2 Transduction 3 Response

Receptor
Activation
of cellular
response
Relay molecules in a signal transduction
pathway

Signaling
molecule
 Concept 11.2: Reception: A signaling
molecule binds to a receptor protein,
causing it to change shape
• The binding between a signal molecule (ligand)
and receptor is highly specific
• A shape change in a receptor is often the initial
transduction of the signal
• Most signal receptors are plasma membrane
proteins
Receptors in the Plasma Membrane
• Most water-soluble signal molecules bind to
specific sites on receptor proteins that span the
plasma membrane
• There are three main types of membrane
receptors
– G protein-coupled receptors
– Receptor tyrosine kinases
– Ion channel receptors
• G-protein-coupled receptor (GPCRs) are the
largest family of cell-surface receptors
• A GPCR is a plasma membrane receptor that
works with the help of a G protein
• The G protein acts as an on/off switch: If GDP is
bound to the G protein, the G protein is inactive
Figure 11.7a

Signaling molecule binding site

Segment that
interacts with
G proteins

G protein-coupled receptor
 Figure 11.7b

G protein-coupled Plasma Activated Signaling Inactive

receptor membrane receptor molecule enzyme

GTP
GDP GDP
CYTOPLASM
G protein Enzyme GDP GTP
1 (inactive) 2

Activated
enzyme

GTP
GDP
Pi

3 Cellular response 4
• Receptor tyrosine kinases (RTKs) are
membrane receptors that attach phosphates to
tyrosines
• A receptor tyrosine kinase can trigger multiple
signal transduction pathways at once
• Abnormal functioning of RTKs is associated with
many types of cancers
 Figure 11.7c

Signaling Ligand-binding site

molecule (ligand)
 helix in the Signaling
membrane molecule

Tyr Tyr Tyr Tyr Tyr

Tyrosines Tyr Tyr
Tyr
Tyr Tyr Tyr Tyr
Tyr Tyr Tyr Tyr Tyr
Tyr

CYTOPLASM Receptor tyrosine Dimer

kinase proteins
1 (inactive monomers) 2

Activated relay
proteins

Cellular
P Tyr Tyr P
Tyr Tyr P Tyr Tyr P response 1
Tyr Tyr P Tyr Tyr P P Tyr Tyr P
Tyr Tyr P Tyr Tyr P P Tyr Tyr P Cellular
6 ATP 6 ADP
response 2
Activated tyrosine Fully activated
kinase regions receptor tyrosine
(unphosphorylated kinase Inactive
dimer) (phosphorylated relay proteins
3 4
dimer)
• A ligand-gated ion channel receptor acts as a
gate when the receptor changes shape
• When a signal molecule binds as a ligand to the
receptor, the gate allows specific ions, such as
Na+ or Ca2+, through a channel in the receptor
 Figure 11.7d

1 2 3

Gate
closed Ions Gate Gate closed
Signaling open
molecule
(ligand)

Plasma
Ligand-gated
membrane
ion channel receptor Cellular
response
 Intracellular Receptors
• Intracellular receptor proteins are found in the
cytosol or nucleus of target cells
• Small or hydrophobic chemical messengers
can readily cross the membrane and activate
receptors
• Examples of hydrophobic messengers are the
steroid and thyroid hormones of animals
• An activated hormone-receptor complex can
act as a transcription factor, turning on specific
genes
Figure 11.9-5
Hormone EXTRACELLULAR
(testosterone) FLUID

Plasma
membrane
Receptor
protein
Hormone-
receptor
complex

DNA

mRNA

NUCLEUS
New protein

CYTOPLASM
Concept 11.3: Transduction: Cascades of
molecular interactions relay signals from
receptors to target molecules in the cell
• Signal transduction usually involves multiple
steps
• Multistep pathways can amplify a signal: A few
molecules can produce a large cellular response
• Multistep pathways provide more opportunities
for coordination and regulation of the cellular
response
 Signal Transduction Pathways
• The molecules that relay a signal from receptor
to response are mostly proteins
• Like falling dominoes, the receptor activates
another protein, which activates another, and
so on, until the protein producing the response
is activated
• At each step, the signal is transduced into a
different form, usually a shape change in a
protein
 Protein Phosphorylation and
Dephosphorylation
• In many pathways, the signal is transmitted by a
cascade of protein phosphorylations
• Protein kinases transfer phosphates from ATP
to protein, a process called phosphorylation
• Protein phosphatases remove the phosphates
from proteins, a process called
dephosphorylation
• This phosphorylation and dephosphorylation
system acts as a molecular switch, turning
activities on and off or up or down, as required
 Figure 11.10

Signaling molecule

Receptor
Activated relay
molecule

Inactive
protein kinase
1 Active
protein

Ph
kinase

o
1

sp
ho
Inactive

ryl
ATP

ati
protein kinase
ADP P

on
2 Active

ca
protein

sca
PP kinase

de
Pi 2

Inactive
protein kinase ATP
3 ADP P
Active
protein
PP kinase
Pi 3
Inactive
protein ATP
ADP P
Active Cellular
protein response
PP
Pi
 Small Molecules and Ions as Second
Messengers
• The extracellular signal molecule (ligand) that
binds to the receptor is a pathway’s “first
messenger”
• Second messengers are small, nonprotein,
water-soluble molecules or ions that spread
throughout a cell by diffusion
• Second messengers participate in pathways
initiated by GPCRs and RTKs
• Cyclic AMP and calcium ions are common
second messengers
 Cyclic AMP
• Cyclic AMP (cAMP) is one of the most widely
used second messengers
• Adenylyl cyclase, an enzyme in the plasma
membrane, converts ATP to cAMP in response
to an extracellular signal