Cell Signalling

lecture 5

BIOSCIENCES
CH 4006
Dr Alina Atif
 Learning Outcomes

During this lecture you should try and...

• Define signal transduction in terms of the change in chemical information from first
messenger, through second messenger(s) and effector(s), to responses
• Explain the basic components of the cyclic AMP signalling pathway
• Describe examples of how cAMP signalling mediates hormone action in certain cells
and the consequent response of the cells (glucose release from hepatocytes and
dilatation of airway smooth muscle

Led by Learning (LbL)

Membrane is a collage of proteins & other molecules
embedded in the fluid matrix of the lipid bilayer

Glycoprotein Extracellular fluid

Glycolipid

Phospholipids
Cholesterol
Transmembrane
proteins
Peripheral
protein
Cytoplasm Filaments of
cytoskeleton
 Cell Signalling
• To make multicellular organisms, cell must
communicate. This communication is mediated
by extracellular signal molecules
• Cells communicate by means of extracellular
signalling molecules that are produced and
released by signalling cells.
• These molecules recognise and bind to
receptors on the surface of target cells.
• These molecules cause a cellular response by
means of a signal transduction pathway.

Led by Learning (LbL)

 Cell Signalling
• Cells in a multicellular organism
communicate through chemical signals.
• Two form of cell signalling: direct and indirect
• Direct signalling when cells communicate
through direct cell-cell contact
• Indirect form, when the signals travel to the
target such as hormones and Local
mediators.
• Hormones act over a long range. While
local mediators are secreted into the local
environment.
Led by Learning (LbL)
Form of cell signalling

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 Cell Signalling
• Cells are stimulated when extra cellular signalling
molecules bind to a receptor
• Each receptor recognises a specific protein (ligand)
• Receptors act as transducers that convert the signal
from one physical form to another.
• Most signalling molecules cannot pass through the cell
membrane. As such, their receptors are in the cell
membrane.
• Small hydrophobic signal molecules can diffuse directly
into the cell cytoplasm. Led by Learning (LbL)
Receptors

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 Discovery of cAMP
• Adenosine 3’,5’-cyclic
monophosphate – the first
second messenger
• Earl Sutherland, 1957
discovered role of cAMP in
mediating the action of
adrenaline on the liver
• Glycogenolysis – glycogen Earl W Sutherland, Jr.
broken down to glucose, Nobel Prize in Physiology
or Medicine 1971
which is released into the “for his discoveries
blood concerning the
mechanisms of the action
of hormones”
http://nobelprize.org/nobel_prizes/medicine/laureates/1971/ Led by Learning (LbL)
 AC – adenylyl cyclase
cAMP pathway
Revision exercise Ligand/first messenger
Place the labels in (e.g. epinephrine/adrenaline)
the correct
spaces
2 adrenoceptor
5’
AMP 
AC
phosphodiesterase   Heterotrimeric G protein (binds GTP/GDP)
s
cyclic AMP

protein kinase A

phosphorylation
of proteins

AT response
P

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Cascade of signalling events

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Glucose release from liver

Example of stress response

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 Stress-induced release of adrenaline
Mental/physical stress
Higher CNS function chromaffin cell (modified postganglionic cell)
Sympathetic outflow
down spinal nerves

ACh N2R
preganglionic nerve

Adrenal gland adrenaline

medulla (on top of kidney) (epinephrine)
released into the blood
(hormone, endocrine secretion)

N2 nicotinic type 2 receptor

Adrenaline is only made in the adrenal medulla (only place where enzyme PNMT found)

Boron & Boulpaep Medical Physiology 5th edition p1062 Led by Learning (LbL)
 adrenaline
2 adrenoceptor - not an ion channel (e.g. NicR) but a G protein-coupled
2R receptor
glycogen synthase
(active) Hepatocyte
Gs LIVER
AC
ATP
cAMP/PKA

ADP
glycogen
synthase
phosphorylase
(inactive)
kinase (inactive)
AT phosphorylase a
P (inactive)
ADP
AT
phosphorylase P glycogen
kinase ADP ATP
(active)
Cyclic AMP - second messenger phosphorylase ADP
PKA – protein kinase A – effector a glucose 1-phosphate
(active)
Effect of adrenaline on the liver – releases glucose into the blood BLOOD glucose
Enzymatic cascades are typical of signal transduction
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cAMP in dilatation of smooth muscle airway
 Summary of signal transduction
• Pathway from first messenger (neurotransmitter, hormone) to
a response (e.g. neuronal excitation, muscle contraction,
exocrine secretion)
– First messengers: e.g. hormones, neurotransmitters, act on
surface membrane receptors1 – e.g. information as ligand
identity, plasma concentration
– Second messengers: small molecules/ions carry/amplify
the signal inside the cell – information as temporal and
spatial distribution of cAMP, cGMP, Ca2+, Inositol
trisphosphate and Diacylglycerol (DAG)
– Effectors: proteins (e.g. kinases, phosphatases, ion
channels) respond to second messengers and cause the
response
Led by Learning (LbL)
 Summary
• Cell to cell signaling allows organisms to coordinate
the activity of a wide variety of different cell types.

• There are many signalling molecules and receptors

• Signalling is endocrine, paracrine, synaptic, or direct
cell
contact

• First messengers act on surface membrane receptors

while the second messengers amplify the signal inside
the cell.

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