SIGNAL

TRANSDUCTION

DESAK MADE WIHANDANI

DEPT. OF BIOCHEMISTRY
FACULTY OF MEDICINE
UDAYANA UNIVERSITY
Multicellular Organisms have BIG Communication Problems

Hey You – divide Oi! We need

now!!! some glucose!

?
Will you
PLEASE stop
dividing!

Come in #7,
your time is up!
 The Solutions

Sorting out the relevant signals from the irrelevant

Receptors with a high degree of specificity

Detecting signals at low concentrations

Receptors with high affinity coupled to an amplification system

Translating diverse signals into a common intracellular

‘language’
 What Signals Do

Cells respond to signals in a variety of ways

Altered metabolism e.g. altered glycogen metabolism in

response to insulin

Excitation e.g. propagation of nerve impulse in response to

neurotransmitters

Growth and Division (mitogenesis) in response to peptide

growth factors

Programmed Cell Death caused by specific ‘death’ factors or

by removal of other essential factors

Altered Gene Expression – e.g. immunoglobulin synthesis in

response to cytokine signals
 SIGNAL TRANSDUCTION

Allow the cell to sense and respond to

signals in the environment and to change
their behavior accordingly

Signals are sensed by a receptor and

change in their form, so that they can
exert their final effect on the cell
 CELL SIGNALING
• THE COMMUNICATION THAT OCCURS
BETWEEN SIGNALING CELLS AND
THEIR TARGET CELLS
• SIGNALING MOLECULES, LIGAND
• RECEPTORS:
- CELL-SURFACE RECEPTORS
- CYTOPLASMIC RECEPTORS
DEFINITION

• Signal
• Receptor
• Second messenger
 SIGNALS

• Any small molecules that binds specifically

to a receptor site
• Start the whole thing
• Signal is what the target cell senses
 SIGNALS

• Signal that enter the cell

(steroids, Vit.D, thyroid hormone and retinoids)
• Signal that exert their effects from outside
the cell
(insulin, glucagon, growth factors, etc)
 RECEPTORS
• Sense the signal and are activated.
Sensing the signal causes a change in the
structure of the receptor
• Receptors recognize a signal molecule
and transmit the signal by activating a
downstream signaling pathway
• The same signal often has a different
effect on different cell types
 RECEPTORS

1. Intracellular/cytosolic receptors
2. Extracellular/ transmembrane/cell
surface membrane receptors
 INTRACELLULAR RECEPTORS
• The signal crosses the membrane and
activates gene transcription.
• Signal for intracellular receptors include
steroid hormones, retinoic acid, thyroid
hormone and vit. D, sex hormones
EXTRACELLULAR/TRANSMEMBRANE
RECEPTORS/ CELL-SURFACE
MEMBRANE RECEPTORS

• Signals that do not enter the cell must be sensed

by a receptor outside that can send the signal
inside. These signals are sensed by
Transmembrane receptors
• Polypeptide hormones (Insulin, glucagon,
growth hormones)
• As first messenger
Second messenger
TRANSMEMBRANE RECEPTORS/ CELL-
SURFACE MEMBRANE RECEPTORS

• These receptors span the membrane.

• 3 large classes of cell surface
receptors; ion channel, a G-protein
linked receptors or an enzyme linked
receptors
 ION-CHANNEL COUPLED
RECEPTORS

• The signal activates the flow of ions

across the membrane
G-PROTEIN COUPLED RECEPTORS

• These activate a G-protein that activates

downstream signals
• G-protein activation usually leads to an
increase in second messenger
concentration
G-protein linked receptor
Without signaling molecule G-
protein is inactive
G-protein binds to receptor when signaling
molecule is present
Reassembly of α subunit with other 2 subunits
reforms inactive G-protein complex
Activation of gene transcription by
cAMP
ENZYME COUPLED RECEPTORS
• Signal activates an enzyme activity of the
receptor itself
• Activation of the receptor turns the
receptor itself into an active enzyme
• Tyrosine kinase: phosphorylate protein
tyrosine residue
• Phospholipase C: cleaves PIP2 into IP3
and DAG
 SECOND MESSENGERS
• Small signaling molecules generated in
respond to extracellular signals. They
amplify and propagate the signal
• Relay the primary signal
• cAMP
• Ca2+
 cAMP
• ACTIVATES cAMP-DEPENDENT
PROTEIN KINASE (A-KINASE):
– REGULATORY COMPONENT
– ACTIVE CATALYTIC SUBUNITS
• R2C2

• PHOSPHORILASE KINASE
• GLICOGEN SYNTHASE
Activation of cAMP dependent
protein kinase
 Activation of cAMP
dependent protein kinase