Presented by Saba Junaid from GCUF

1. Advanced Biochemistry
Assignment # 01
Topic :
Cell signalling pathway
Submitted by:
Saba Junaid
Roll no:
4845
Semester :
3rd
semester (Morning)
Course:
Bs. Biotechnology
Submitted to:
Dr. Habib Ullah Nadim
Department :
Bioinformatics and Biotechnology

2. CELL SIGNALING PATHWAYS
Cell signalling is a molecular process in which one cell communicate with other cells. It
often control the activity of cellular functions.
Higher multicellular life is way complex than our thinking they are not like unicellular that
are dependent on only single cell. Functioning of organism depends upon the functioning of
individual cells. Individuals cells communicate with one another in variety of ways to sustain
the life of that organism.
Like in human body different organs communicate with one another to bring about a function
that is important for human body. For example if we talk about digestive system this system
is the collection of different organs like stomach, intestines, liver, pancreas. We cannot say
that digestive system contain only stomach. All these organs communicate with one another
accordingly and bring about the digestion of food that we eat and provide energy to humans
cells and tissues.
Likewise cells communicate with one another they send and receive signals and carryout
some important processes in organisms bodies.
Definition:
Various diverse events or processes occur between cell stimulation and final
response are called cell signalling pathway.
Brief History of cell signalling:
Discovery of cellular signalling dates back in 1855.
 In 1855 Claude Bernard described that how secretions from ductless glands into blood
stream can affect the cells that are far from the origan of these secretions.
 In 1970, Martin Rodbell observed the effect of glucagon on liver cell membrane
receptors of rat liver.
He revealed about guanosine triphosphate and stimulated G protein role in cell metabolism.
Definition of cellsignalling:
Cell signalling is a biological process in which one cell
communicate with other cells, send, and receive signals and helps in coordination in
multicellular organisms. It is fundamental process in biology for coordination with rest of
body.
Signal:
Signal is a message that carry information in it. Cells communicate with one another
in the form of signals. Signals transfer information from cell to cell. Every biological process
and complex in nature and involve a lot of signals to carry out the processes.
Ligand and receptors:
Ligand is a specific molecule that bind to the receptor side of cell.
Receptor is the side of cell that detect specific ligand and bind that ligand to the receptor side.

3. Every ligand binds to specific receptor side that is present on specific cells. If appropriate
receptor is not present to the cell the ligand cannot bind to that cell.
Signaltransduction:
This refers to the presence of signal in the environment outside the cell
that can induce the change in intracellular state without crossing the cell membrane.
This is a diagram showing that only a specific cell this specific receptor can recognize
specific ligand and bind with it.
Why cell communicates?
Cell communicate to bring about the following useful
processes.
 During the process of development cell differentiate into specialized cells to perform
specific role.
 Cells communicate to receive the message for their fate, whether they are going to
live, or they will die.
 They communicate to regulate metabolism of cell.
 They communicate to transfer nerve impulse and involve in neurotransmission.
 They help in movement by contraction and relaxation.
 They communicate to bring about development and expression of secondary sex
characters.
Modes of signalling:
There are many modes of cell communication. Cell may
communicate with one another by:
 cytoplasmic bridges
 signalling by secreting molecule

4.  signalling by plasma membrane molecules
Signalling by gap junction:
Gap junctions are intracellular cannels that that allow
cell to cell transfer of ions and small molecules. Gap junctions connect the cytoplasm
of two cells and help in the direct communication of two cell.
Signalling by Secretion:
 This figure shows the communication by secretion of molecules.

5. Membrane signalling:
 This figure is showing communication by membrane signalling.
Cascadeofcell communication:
Following are the steps that are involved in cell signalling process.
Synthesis of signalling molecule
Release of signalling molecule
Transport of signal to target site
Effect of signalling molecule
Response
Termination of signal

6. Classification of cell communication
Cell communication is broadly classified into two classes.
 Extracellular communication
 Intracellular communication
Classification of intracellular communication:
There are 4 ways by which cell communicate with other cells. They are following.
 Paracrine signaling
 Endocrine signaling
 Autocrine signaling
 Juxtracrine signaling
Paracrine signaling:
In paracrine signaling, signaling molecule released by cell affect only
those cell that are close to it. Paracrine signaling is a type of communication in which cell
produces a signal that affect or induce changes in nearby cells. This mode of signaling is
short ranged. This may induce change or alter behaviour of that cell.
Signal that is released from signaling molecule is called ligand. Nearby cells respond to this
ligand. But this is short, ranged communication. This ligand can diffuse only over small
]distance and affect nearby cells. Not only this mode of communication is short ranged but
also for short time.
This figure is showing Paracrine signaling mode, which secretory cell is
secreting the signal or ligand which in tune affecting neighbour cell.

7. Example of paracrine signaling:
Basically in Paracrine signaling, signals are transfer to nearby
cells. One such is the conduction of nerve impulse across synapses. If a signal released from a
neuron it will only affect those neurons that are near to it.
In this case signal in neurotransmitter that is released from presynaptic membrane and
absorbed to the post synaptic membrane. In this case neurotransmitter affect only neuron near
to it. In this way by paracrine signaling nervous coordination occurs. Our brain, control
centre controls the system by paracrine signaling. Signal released from one neuron will affect
the next neuron near to it and message is conducted towards the brain by the coordination of
neurons in series and by paracrine signal.
These signals also involved in action potential and resting membrane potential of nerve
impulse.
 This figure explains the paracrine signaling at synapsis.
Blood clotting by paracrine signaling:
Growth factors and clotting factors are paracrine signaling molecules. These factors travels to
the organs and then stimulate them to bring about the growth and blood clotting process.

8. When blood vessel is damaged from a certain area this means its endothelial lining is damaged
or broken. After endothelium is braked it start releasing a chemical called von Willebrand
factor, this will bind to the platelets, this is done through paracrine signaling process.
Meanwhile collagen fibre bind to the platelets and after complex series f reaction fibrin starts
threading the wound site and make a clot there.
Endocrine signalling:
This signaling method involves the secretion of hormones, and signal
can affect the cells that are very far from it. It can affect the molecules that are at very large
distance from the signaling cell.
This signal is always released from an endocrine glands and signal is called hormone. A
hormone is always secreted by a gland. It is transmitted to the site of action or target cell with
the help of blood. Signals are released into the blood and blood carry this hormone to the target
cell. There are 20 different kind of endocrine glands into the human body.
Some endocrine glands:
 Thyroid gland
 Pancreases gland
 Thymus gland
 Adrenal gland
 Pituitary gland
 Uterus
 Testes
 Ovaries
 Pineal glands
These glands secret different kind of hormones like oxytocin, oestrogen, epinephrine, nor
epinephrine, glucagon, insulin, testosterone, and gonadotropins etc. these are also called
ductless glands, because secretions are directly poured into blood.
These hormones are released by the arrival of specified stimulating factor and then after
stimulation these hormones are secreted into blood stream and then carried to the target site.

9. Example of endocrine signaling:
One such example of endocrine signaling is insulin and
glucagon secretion from pancreases. When we eat, the food is metabolised into digestible
practical this produce glucose. Glucose level increase after meal. Normal level of glucose in
blood in 0.08%. If glucose level exceeds this value insulin is secreted by B cells of pancreases,
insulin balance the glucose level by converting extra glucose in the form of glycogen. This
glycogen is stored in the liver.
But if the level of glucose is decreased in blood then pancreas release glucagon released from
a this will break liver stored glycogen into glucose. Both hormones are antagonistic to each
other.
Difference between paracrine and autocrine signaling:
Differences Paracrine signaling Endocrine signaling
Target cells Near to the site of production. Far from the site of
production.
Action time Generally fast and quick. Usually slow and long
lasting.
Route Signals are Directly released
into the surrounding.
Signals are released into the
blood.
Ligand Chemical or neurotransmitter. Hormones.
Important Both both
 Figure showing the difference of paracrine and endocrine signaling, autocrine
signalling and direct signaling.

10. Autocrine signaling:
It is a type of cell signaling in which signals released from cell start
affecting the same cell. In this signaling mode same cell in secreting signal and that cell is also
receiving it. Substance secreting from cell can provoke reaction by itself.
This word is derived from a Greek prefix, auto, meaning self. It means the cell produce a signal
and then in turn affected by it, change occurs in a cell by its own signal. Signaling molecule is
known as local mediators because it can affect only cells in its mediated range.
Example of autocrine signaling:
In autocrine signaling receptors are present on same
cell that are producing that signal. An example of this signalling is cytokine interleukin 1 in
monocytes. When interleukin 1 is produced in response of external stimuli, it can bind to cell
surface receptors on the same cells that produce it. Cancer cells also show this type of signaling.
Another example is the growth factor that is produced from a cell and in turn affect the same
cell as a result.
 Figure showing autocrine signaling, the signal affecting the cell producing it.

11. General steps in cell signalling:
Juxtracrine signalling:
It is a type of cell-cell or cell-extracellular matrix signaling in
multicellular organisms that require close connection. Two cells make physical connection.
The receptor present on the membrane of the other cell that is very near to it. Its communicates
with other cells by gap junctions. Signals producing cell release signals that are received by
cells next to it. This mode of signaling is also called membrane to membrane communication.
 Figure showing juxtracrine signaling.
Reception
Transduction
Response

12. Example of juxtracrine signaling:
The notch signaling mechanism is also the example of
juxtracrine signaling. It is also known as contact dependant signaling. In this type two cell
make physical connection between them, to communicate. This direct contact allow then to
control the process of cell differentiation during embryonic development.
In worms two cells of developing gonads have equal chance to develop into uterus. The
decision that which cell will continue to divide depends upon the surface signaling. One cell
will produce more surface protein than other and activates notch receptor to adjacent cell. This
activates a system that reduce notch expression on other cell that otherwise will differentiate.
Now notch containing cell become uterus.
 Figure showing juxtracrine signaling mode.
Signal transduction pathways:
Following are the pathways
1. Signal recognition:
 ligand binding occurs

13.  cell connects
2. Signal transduction:
 transfer of signal to the interior
 Modulate the activity of protein kinase and phosphatases
3. Response:
 phosphorylation state of target,
 modulation of affecter activity
 reversibility of response
Receptor activation:
 Cellular responses
 Permeability
 Metabolism
 Secretory activity
 Rate of proliferation and differentiation
 Contraction

14. Lipid soluble messengers:
 Glucocorticoids:
This activates numerous genes that are involved in cellular metabolism.
 Cortisol
Inhibitory for those genes whose protein products are inflammatory
mediators.
Ligand gated ion channels:
Nervous proteins act as ion channels.
 Junctions between nerves
 Neuromuscular junction
 Figure showing a junction between two nerves. This is paracrine signaling mode.
Cytokines receptor:
There are some regulatory proteins. This receptor have no enzymatic
activity their enzymatic activity lie in the family of separate cytoplasmic kinases. Cascade of
phosphorylation leads towards the cellular responses of stimuli.
These receptors are mainly involved in immunity. These receptors are may be membrane
bounded or soluble. Soluble cytokines receptors are the common regulators of cytokine
function. These receptors are consisted of extracellular area of membrane bounded receptors

15. Pathways of channel activation:
Conclusion:
As far as cell signalling is a complex biological process that is occurring through different ways
and by different mods and routes. This brief study show the complexity of life, importance of
communication between cell and different processes that are occurring in the body of living
organism. This shows us that how beautifully and how carefully ALLAH has created us.
Ligand binds to
the ion channel
Opening of ion
channel
Increased
diffusion across
membrane
Change in
electrical chargeCell responseContraction or
conduction