TRƯỜNG ĐẠI HỌC DƯỢC HÀ NỘI

KHOA CÔNG NGHỆ SINH HỌC

Signal Transduction

PGS. TS. Phùng Thanh Hương

Objectives

• To present concepts of signal and signal transduction

• To present key players in a signal transduction pathway

CONTENT

• What is a cell signal?

• What is signal transduction?

• What are Key players of Signal Transduction?

 1. What is a signal?
• Signals are chemicals and physical stimuli that trigger cellular response with

changes that can affect cell function or development

• Most signals are chemical molecules

 Signal molecules
- Small molecules (adrenaline, acetylcholine)
Many drugs are
signaling molecules
- Peptides/Protein (glucagon, insulin, growth

hormone)

- Steroids (cortisol, testosteron)

- Gases (NO, O2)

 Signal molecules
Signaling molecules can be synthesized from inside, packed into secretory

vesicles/extracellular vesicles and exported to outside of the cells

 Cell communication
• Many types of signaling molecules are released by

one cell and induce a response in a different cell 

Cell communication

• In unicellular organisms, extracellular signaling

molecules regulate interactions between individuals

• In multicellular organisms, they mainly regulate

physiology and development.

Classification of
signaling

• Endocrine signaling: hormones

• Paracrine signaling:

neurotransmitters

• Autocrine signaling: tumor cells,

cultured cells
 ADRENALINE:
Classification of Neurotransmitter  ↑ Heart
signaling rate, blood pressure, heighten
awareness

• Adrenaline/epinephrine: neuro

transmitters and hormone;

paracrine/endocrine signaling

ADRENALINE:
Adrenal hormone 
Carbohydrate metabolism  Fight or Flight
Blood glucose level ↑
 Indicated in
emergencies such as
shocks
2. What is Signal Transduction?

• The overall process of converting

extracellular signals into intracellular

responses, as well as the individual

steps in this process

• 3 phases: reception  transduction 

response
Fig. 11-6-1

Signal Transduction
EXTRACELLULAR CYTOPLASM
FLUID
Plasma membrane

1 Reception

Receptor

Signaling
molecule
Fig. 11-6-2

Signal Transduction
EXTRACELLULAR CYTOPLASM
FLUID
Plasma membrane

1 Reception 2 Transduction

Receptor

Relay molecules in a signal transduction pathway

Signaling
molecule
Fig. 11-6-3

Signal Transduction
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

What is the characteristics of each step of signal

transduction?
3 Phases of Signal Transduction - Reception

• Reception: A signal molecule (ligand)

binds to a receptor protein, causing it

to change shape

• The binding between a signal molecule

(ligand) and receptor is highly specific

and with high affinity

 3 Phases of Signal Transduction - Reception

• Ligand-Receptor binding:

- multiple weak, noncovalent forces

(i.e., ionic, van der

Waals, and hydrophobic interactions)

- molecular complementarity

• Each type of receptor binds only a

single type of signaling molecule or a
group of very closely related ones.
3 Phases of Signal Transduction - Reception
• A shape change in a receptor is often the initial transduction of the signal

Nicotinic Acetylcholine receptor

3 Phases of Signal Transduction - Reception

↑muscle contrac on

• Different cell types often have

different receptors for the same

↓ the rate of
contraction and heart
ligand, and activation of each Acetylcholine rate

receptor type induces a different

intracellular signal transduction ↑ secre on

Adverse Drug of the digestive enzymes
Reactions
pathway  different effects (ADRs)
3 Phases of Signal Transduction - Transduction
• Transduction: Cascades of molecular

interactions to deliver signals from

receptors to target molecules in the

cell

• Signal transduction usually involves

multiple steps
3 Phases of Signal Transduction - Transduction
• Multi-step pathways can amplify the Effects
of Extracellular Signals: A few molecules can
produce a large cellular response

• amplification enable activation of a relatively

small number of cell-surface receptors to
trigger major changes in cell metabolism,
movements, or gene expression.

• Signal transduction rate and efficacy

3 Phases of Signal Transduction - Transduction
• 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
3 Phases of Signal Transduction - Transduction
• At each step, the signal usually induces a
shape/structure change in a protein
• In many pathways, the signal is transmitted by a
cascade of protein phosphorylation by Protein
kinase enzymes
• 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  Cell Regulation
3 Phases of Signal Transduction - Transduction
• Many signaling pathways regulate protein synthesis,
usually by turning genes on or off in the nucleus.

• The final activated molecule may function as a

transcription factor  gene expression modified

• Protein changes in structure/quantity 

Inhibition/Activation
3 Phases of Signal Transduction - Response

An example of response
of the body after a signal
that you can sense/
measure?
3 Phases of Signal Transduction - Response

• Result of a signaling pathway is the

activation/inhibition of a final reaction  new
product that has a specific effect
3. What are Key players of Signal Transduction?

Effector Second
proteins messenger

Receptor
3. What are Key players of Signal Transduction?
• Definition: A protein inside or on the surface of a cell
Receptor that binds to a specific ligand, transduce signals, and
causes a specific effect in the cell.

• Classification:

Membrane receptors

G protein-coupled receptors

Receptor tyrosine kinases

Ion channel receptors/Ionotropic receptor

Intracellular receptors
Key players of Signal Transduction
• Some receptor proteins are intracellular, found in the
Intracellular
Receptor cytosol or nucleus of target cells

What kind of signal can bind to intracellular receptors?

• Small or hydrophobic chemical messengers can readily

cross the membrane and activate receptors (steroid and
thyroid hormones)

• An activated hormone-receptor complex can act as a

transcription factor, turning on specific genes  protein
Fig. 11-8-1
Hormone EXTRACELLULAR
(testosterone) FLUID

Plasma
membrane
Receptor
protein

DNA

NUCLEUS

CYTOPLASM
Fig. 11-8-2
Hormone EXTRACELLULAR
(testosterone) FLUID

Plasma
membrane
Receptor
protein
Hormone-
receptor
complex

DNA

NUCLEUS

CYTOPLASM
Fig. 11-8-3
Hormone EXTRACELLULAR
(testosterone) FLUID

Plasma
membrane
Receptor
protein
Hormone-
receptor
complex

DNA

NUCLEUS

CYTOPLASM
Fig. 11-8-4
Hormone EXTRACELLULAR
(testosterone) FLUID

Plasma
membrane
Receptor
protein
Hormone-
receptor
complex

DNA

mRNA

NUCLEUS

CYTOPLASM
Fig. 11-8-5
Hormone EXTRACELLULAR
(testosterone) FLUID

Plasma
membrane
Receptor
protein
Hormone-
receptor
complex

DNA

mRNA

NUCLEUS New protein

CYTOPLASM
Key players of Signal Transduction
Membrane
What kind of signal can bind to intracellular receptors?
Receptor
• Most water-soluble signal molecules bind to specific sites on receptor
proteins in the plasma membrane

• Ligand binding  a conformational change in the receptor  activation of

intracellular signal transduction pathways that ultimately modulate cellular
metabolism, function, or gene expression
Three types of membrane receptors

GPCR TKR

Ionotropic
Receptor
Key players of Signal Transduction
Membrane
Receptor

G Protein - Coupling Receptor

(GPCR)
• The most numerous class of
receptors
• Ligand: neurotransmitters,
hormones, photons of light...
• ~ 30 of all drugs used in humans
are agonists or antagonists of
specific GPCRs
Key players of Signal Transduction
Membrane
Receptor

Tyrosine kinases Receptor (TKR)

• Membrane receptors that attach
phosphates to tyrosine
• A receptor tyrosine kinase can
trigger multiple signal
transduction pathways at once
• Ligands: growth factors,
hormones
Key players of Signal Transduction
Membrane
Receptor
Ion channel receptor/ Ionotropic receptor

• A ligand-gated ion channel receptor acts as a

gate when the receptor changes shape

• When a ligand binds to the receptor, the gate

allows specific ions, such as Na+ or Ca2+,
through a channel in the receptor

• Ligands: neurotransmitters, toxins (venom)

Key players of Signal Transduction
• Signal transduction pathway: The chain of intermediates (second messengers,
effector proteins)
Effector • Proteins are already in cells
proteins • Protein are not available, needed to be synthesized

Second • nonprotein, low Mw intracellular molecules which relay

messenger and often amplify the signal of the “first messenger”

First
messenger?
Key players of Signal
Transduction

Effector
proteins

Second
messenger
Key players of Signal Transduction
Second • Second messengers are small, non-protein, water-
messenger
soluble molecules or ions that spread throughout a cell
by diffusion

• Binding of ligand to cell-surface receptors often results

in a rapid increase (or, occasionally, decrease) in the
intracellular concentration of these ions or molecules.

• Cyclic AMP and Ca++ are common second messengers

Key players of Signal Transduction

cAMP

Many signal molecules trigger formation of

cAMP

cAMP usually activates protein kinase A, which

phosphorylates various other proteins
Key players of Signal Transduction
Cytosolic
Ca++

• [Ca2+] in the cytosol is kept very low (~10-7 M) by ATP-powered

pumps that continually transport Ca2+ out of the cell or into the
endoplasmic reticulum (ER)/ Mitochondria

• Cytosolic Ca2+ concentration can be increased from tenfold to a

hundredfold by a signal-induced release of Ca2+ from the ER lumen
or the extracellular environment by the opening of calcium
channels

• Muscle: contrac on ↑

• Beta cells: insulin secretion