Signal Transduction
M. M. Hamdi
13-09-2013
9.00am-10.00am
Outline of This presentation
This lecture gives an idea about:
What is signal transduction also
known as cell signaling
Basic mechanisms used for cell
signaling
At the end of this lecture you should be
able to:
1) Explain hormones and receptors and
its role in extracellular signaling.
How do cells transmit signals
2) List the steps in the process of
extracellular signaling.
Steps in the process of
extracellular signaling.
3) Discuss the classification of
extracellular signaling.
Tools for cell signaling
4) Discuss the overview of extracellular
signals.
Basic Components cell signaling
Relevance of signal transduction
in medical science.
Note: Extra reading & thinking helps in
exam and gives you idea on the power of
signal transduction in medical sciences
Introduction
Human is a multicellular being.
There are about 10, 000 000, 000 000cells (10trilion cells) in the body
for example hepatocytes, myocytes, leukocytes, RBC, WBC and so
on making up 210-411 types of cells in the body.
10 X of these stacks !
Introduction
Living cells are dynamic
performing various functions
including biochemical
reaction, growth, division, cell
death.
Therefore those functions are
coordinated at cellular level.
Signal transduction or cell signaling
The basis for this coordination are:
1) Extracellular or intercellular cell
signaling, or communication
between cells. This communication
allows single cell to influence
behavior of other cells in a specific
manner.
2) Intracellular signal transductionan intracellular events which affects
intracellular biochemical reactions.
The basic mechanisms used for signal
transduction
a) Communication via intercellular messenger.
eg; In low level of thyroid hormone
Anterior pituitary secretes TSH.
Through blood flow it was sensed
by TSH-R on thyrocytes
which then secretes Thyroxin.
Another example;
In water deprivation
(plasma osmolality increase)
Posterior pituitary secretes ADH
Through blood flow it was sensed
by ADH-R on kidney cells which then
decreases water excretion.
continuation
b) Communication via Gap junction.
eg. A connection between one cell and another,
eg. Gap junction between smooth muscle cell in GIT
-allows ions movement for electrical activity,
-allows movements of metabolites
from one cell to another cells.
Another example
Cardiac muscle use the similar mechanism
to maintain unison contraction.
c) Communication via surface protein.
eg. Direct communication between cells
Integrin receptor for cell migration
Another example;
Cell adhesion uses integrin receptor
Tutorial
Regarding the basic mechanisms used for intercellular signal transduction in
the diagram above
a) Intercellular messenger (T/F)
b) Gap Junction (T/F)
c) Surface protein (T/F)
In diagram a) above
State one intercellular messenger _________
State the site which the intercellular messenger binds __________
State one effect of the intercellular signal transduction in a) above _________.
How do cell transmit signal?
Consider endocrine system where
sensor and effector are apart-blood
circulation. But there are situations
when cells stimulates itselfautocrine. Cells can also stimulate
neighbouring cells-paracrine eg.
during infection
Consider rapid reflex eg. touching
of hot surface- rapid electrical
signal jump on the myelin sheath
Consider information that travels
through neurons vision-eyes-tobrain-to effector organsynaptic
signaling
DNA
Prepare
mRNA
Protein
Steps of cellular signaling
These are common steps for cellular signaling:
Signal (known as first messenger) ie. synthesised/released then transported to target cell.
(1)Upon receiving a signal (such as growth factor which for growth), a membrane bound receptor becomes activated.
(2)This in turn results in changes in cellular metabolism which transmit the signal further downstream. As to transmit
the signal further downstream the activated receptor passes the signal onto components signal usu. Signaling
proteins which can be activated or deactivated.
(3)This in turn results in changes in cellular metabolism which elicit response required by the cell such as
proliferation, survival, hypertrophy and so on.
Finally signal attenuated which then terminates the response
Steps of cellular signaling
Tools for Cell Signaling
Signaling proteins are tools for cell signaling for example:
a)Receptor
-for detection of incoming signal
-GPCR largest family of membrane bound receptor have no
cytoplasmic tyrosine kinase domain (use G-protein for activation)
- RTKs such as EGFR requires activation have
phosphorylatable region (also known as tyrosine kinase
region)
-note that not all receptor are membrane bound eg. Androgen receptor
b)Protein kinase-attaches phosphate
to signaling proteins
(phosphorylation) = activates
c)Protein phosphatase
-removes phosphate from signaling
proteins
(dephosphorylation) = deactivates
This is how signaling
molecules are reversibly
being
activated/deactivated.
d)Regulatory GTPase
-function as switches and exist in active form to transmit signal;
in inactive form-repress signal further downstream
e)Adaptor proteins
-mediates signal transmission between signaling proteins
Relevance of cellular signaling in
medical sciences
16.4% of total
genes
involved
in
signal
transduction
Relevance of cellular signaling in
medical sciences
-Intercellular signaling involve in homeostasis such as;
Maintaining hormone level
through feedback mechanism
Thyroid hormone
Steroid
hormone
such
glucorticoid
Oxytocin-uterine contraction
Blood glucose by insulin
as
Maintaining population of healthy cells
through apoptosis
Etc.
Example of a feedback mechanism
Hypothalamo-pituitary-thyroid axis
Relevance of cellular signaling in
medical sciences
-Intracellular signaling protein form modules which makes up
signaling pathways
-Signaling pathways:
Regulates various physiological functions such as;
Intracellular Calcium release for muscle
contraction.
Paracrine signaling by Nitric Oxide in smooth
muscle
Cell motility
Creating new blood vessel eg. Notch receptor
Contact inhibition
Etc.
Modulates numbers of physiological function such as
phosphorylation of Myosin light chain in smooth
muscle contraction.
Too many signaling pathways which its physiological
functions are not known.
Potential on going researches to characterize
signaling pathways to a particular physiological
function. As to understand, manipulate and create
new drug/treatment.
References
Krauss G.(2003). Biochemistry of
signal transduction and regulation 3rd
edition
Molecular Cell Biology (2000). Lodish
et. al. 4th edition.
Any cell biology, molecular biology or
biochemistry textbook.
