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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 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