Signal Reception

The initiation of transduction

LE 11-7aa

Signal-binding site

Segment that
interacts with
G proteins

G-protein-linked receptor
 G-Protein-Linked Receptors
• Used by many different signal molecules
including:
– Yeast mating factors
– Epinephrine
– Many other hormones
– Many neurotransmitters
 G-Protein-Linked Receptors
• The receptor is a single polypeptide with 7
alpha helices
• It works in conjunction with a G-protein and
another protein, usually an enzyme
 G Protein
Signal-binding site

Figure 11.7
Segment that
interacts with
G proteins

G-protein-linked Activated Inactivate

Plasma Membrane Signal molecule
Receptor Receptor enzyme

GDP
G-protein GDP GTP
CYTOPLASM (inactive) Enzyme

Activated
enzyme

GTP
GDP
Pi

Cellular response
 How it works
• 1) The signal molecule (ligand) binds to the
receptor. The receptor changes shape and
activates the G-protein.
• 2) GTP replaces GDP on the G-protein.
• 3) The active G-protein binds to and activates
the enzyme. This starts the pathway leading
to the cellular response.
• 4) Ligand detaches; all proteins go back to
being inactive.
 G Protein
Signal-binding site

Figure 11.7
Segment that
interacts with
G proteins

G-protein-linked Activated Inactivate

Plasma Membrane Signal molecule
Receptor Receptor enzyme

GDP
G-protein GDP GTP
CYTOPLASM (inactive) Enzyme

Activated
enzyme

GTP
GDP
Pi

Cellular response
 Tyrosine Kinase Receptors
• Are the receptors for most growth factors
• Often activate several different signal-
transduction pathways at once
 LE 11-7b

Signal Signal-binding site

molecule
a Helix in the Signal
membrane molecule

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

Receptor tyrosine
kinase proteins Dimer
CYTOPLASM (inactive monomers)

Activated relay
proteins

Cellular
Tyr Tyr P Tyr Tyr P P Tyr Tyr P response 1
Tyr Tyr P Tyr Tyr P Tyr Tyr P
P
Tyr Tyr P Tyr Tyr P P Tyr Tyr P Cellular
6 ATP 6 ADP response 2

Activated tyrosine- Fully activated receptor

kinase regions tyrosine-kinase
(unphosphorylated (phosphorylated Inactive
dimer) dimer) relay proteins
 Tyrosine Kinase Receptors
• Consists of two polypeptides
• Each is part receptor, part enzyme
 Tyrosine Kinase Receptors
How they work:
• 1) Signal molecules attach
• 2) The two polypeptides aggregate and form a
dimer
• 3) They phosphorylate the tyrosines on the other
polypeptide.
• 4) Now fully activated, they can bind to
intracellular proteins which initiate a signal
transduction pathway.
• 5) Several different pathways can be activated at
once.
 LE 11-7b

Signal Signal-binding site

molecule
a Helix in the Signal
membrane molecule

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

Receptor tyrosine
kinase proteins Dimer
CYTOPLASM (inactive monomers)

Activated relay
proteins

Cellular
Tyr Tyr P Tyr Tyr P P Tyr Tyr P response 1
Tyr Tyr P Tyr Tyr P Tyr Tyr P
P
Tyr Tyr P Tyr Tyr P P Tyr Tyr P Cellular
6 ATP 6 ADP response 2

Activated tyrosine- Fully activated receptor

kinase regions tyrosine-kinase
(unphosphorylated (phosphorylated Inactive
dimer) dimer) relay proteins
 Ligand Gated Ion Channels
• Are protein pores in the plasma membrane
that open or close in response to a chemical
signal.
• 1) Signal binds
• 2) Channel opens and ions flow through; cell
responds
• 3) Ligand dissociates; channel closes
• Ex. neurons
LE 11-7c
Signal Gate
molecule closed Ions
(ligand)

Plasma
Ligand-gated
membrane
ion channel receptor

Gate open

Cellular
response

Gate closed
 Second Messengers
• Are small, non-protein, water-soluble
molecules or ions.
• The signaling molecule is always the ‘first
messenger’.
• Second messengers participate in pathways
involving G-protein linked receptors and
tyrosine kinase receptors.
 Second Messengers
• The most commonly used 2nd messenger is
cAMP (cyclic AMP).
• ATP is converted to cAMP by a membrane
enzyme, adenylyl cyclase, in response to an
extracellular signal.
• cAMP usually activates protein kinase A,
which phosphorylates various other proteins.
LE 11-10

First messenger
(signal molecule
such as epinephrine)
Adenylyl
G protein cyclase

G-protein-linked GTP
receptor

ATP
Second
cAMP messenger

Protein
kinase A

Cellular responses
 Second Messengers
• Other important 2nd messengers include Ca2+
ions, IP3, and DAG.
• Many signal transduction pathways involve a
phosphorylation cascade in order to get the
final cell response.
LE 11-13
Reception

Binding of epinephrine to G-protein-linked receptor (1 molecule)

Transduction

Inactive G protein

Active G protein (102 molecules)

Inactive adenylyl cyclase

Active adenylyl cyclase (102)

ATP
Cyclic AMP (104)

Inactive protein kinase A

Active protein kinase A (104)

Inactive phosphorylase kinase

Active phosphorylase kinase (105)

Inactive glycogen phosphorylase

Active glycogen phosphorylase (106)

Response
Glycogen
Glucose-1-phosphate
(108 molecules)
LE 11-14
Growth factor
Reception
Receptor

Phosphorylation
cascade
Transduction

CYTOPLASM

Inactive
transcription Active
factor transcription
factor Response
P

DNA

Gene

NUCLEUS mRNA