Cell Signaling is a phenomenon in which cells receive and respond to the signals or chemical messages from their internal environment or from the neighbouring cells.

1. Cell Signaling
Archana Das, M.Sc.
Tangla College

2. What is Cell Signaling ?
Cell Signaling is a phenomenon in which cells receive and
respond to the signals or chemical messages from their
internal environment or from the neighbouring cells.
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3. Cells typically communicate using chemical signals. These
chemical signals, which are proteins or other molecules like
G-Protein-Linked Receptors (GPCR), produced by a sending
cell, are often secreted from the cell and they are released
into the extracellular space.
In order to detect a signal a target cell must have the
right receptor for that signal. When a signaling molecule
binds to its receptor, it alters the shape or activity of the
receptor, triggering a change inside of the cell.
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4. Signaling Molecules
Cell Signaling molecules are also called as LIGANDS.
The message carried by a ligand is often relayed through a chain of
chemical messengers inside the cell.
The Signaling Molecules may be:
1) Hormones from Endocrine glands
2) Neurotransmitters
3) Nitric Oxide
4) Carbon monoxide
5) Certain Plant Hormones and
6) Eicosanoids

5. Cell surface receptors are some membrane
receptors or transmembrane receptors that
are embedded in the plasma membrane of cells.
They act in cell signaling by
receiving extracellular molecules. They are
specialized integral membrane proteins that
allow communication between the cell and
the extracellular space.
The extracellular molecules react with the
receptor to induce changes in
the metabolism and activity of a cell. In the
process of signal transduction, ligand
binding affects a cascading chemical
change through the cell membrane
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6. Methods of Cell Signaling
Cell Signaling in organisms involve mainly two forms. They are :
1) Cell To Cell Signaling
2) Signaling by Secreted Molecules
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7. Cell To Cell Signaling
Cell To Cell Signaling involves direct transmission of a signal from a
sending cell to a receiving cell. Gaps between two cells in animals are
tiny channels that directly connect neighboring cells. These water-filled
channels allow small signaling molecules, called intracellular mediators,
to diffuse between the two cells.
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8. There are four basic categories of
Chemical Signaling found in multicellular
organisms. They are :
1) Paracrine signaling
2) Synaptic signaling
3) Endocrine signaling and
4) Autocrine signaling
Signaling by Secreted Molecules
(Chemical Signaling)
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9. Paracrine Signaling
Cells that are near one another
communicate through the
release of chemical messengers
called ligands that can diffuse
through the space between the
cells. This type of signaling, in
which cells communicate over
relatively short distances, is
known as Paracrine Signaling.
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10. Synaptic signaling
One unique example of synaptic signaling is seen in the
transmission of impulses through the synapse, the junction
between two nerve cells.
When the sending neuron triggers an electric impulse,
it moves rapidly through the cell traveling down the
long axon. When the impulse reaches the synapse, it
triggers the release of ligands called neurotransmitter
(Acetylcholine), which quickly cross the small gap
between the nerve cells. When the neurotransmitters
arrive at the receiving cell, they bind to receptors and
cause a chemical change inside of the cell
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11. Endocrine Signaling
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When cells need to transmit signals over long
distances, they often use the circulatory system as
a distribution network for the messages they send.
In long-distance Endocrine Signaling, signals are
produced by specialized cells and released into the
bloodstream, which carries them to target cells in
distant parts of the body. Signals that are produced
in one part of the body and travel through the
circulation to reach far-away targets are known
as Hormones.
For example, the pituitary releases growth
hormone to promotes growth. Like most
hormones, GH affects many different types of cells
throughout the body. However, cartilage cells
provide one example of how GH functions: it binds
to receptors on the surface of these cells and
encourages them to divide.

12. Autocrine signaling
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Autocrine signaling is important during
development, helping cells to take on and reinforce
their correct identities.
From a medical standpoint, autocrine signaling is
important in cancer and is thought to play a key
role in metastasis, i.e., in the spread of cancer from
its original site to other parts of the body
In many cases, a signal may have both autocrine
and paracrine effects, binding to the sending cell as
well as other similar cells in the area.
In Autocrine Signaling, a cell
signals to itself, releasing a ligand
that binds to receptors on its own
surface or depending on the type
of signal, it can bind to receptors
inside of the cell.

13. RECEPTORS IN CELL SIGNALING
Receptors are of many types. But signaling
receptors can be divided into two categories:
1) Intracellular Receptors:
They are found inside of the cell
i.e., in the cytoplasm or nucleus of the cell.
2) Cell surface receptors:
They are found in the plasma membrane.
Archana Das

14. Intracellular Receptors
Archana Das
Intracellular receptors are
receptor proteins found on the
inside of the cell, typically in
the cytoplasm or nucleus. In
most cases, the ligands of
intracellular receptors are
small, hydrophobic molecules,
since they must be able to
cross the plasma membrane in
order to reach their receptors.
For example, the primary
receptors for hydrophobic
steroid hormones, such as the
sex hormones estradiol
(estrogen) and testosterone,
are intracellular.

15. Archana Das
Cell Surface Receptors
Cell Surface Receptors are membrane anchored proteins that bind to
ligands on the outside surface of the cell. In this type of signaling, the
ligand does not need to cross the plasma membrane. Many different kinds
of molecules may act as ligands.
A typical cell-surface receptor has three different domains, or protein
regions: They are :
1) A Extracellular Ligand-Binding Domain,
2) A Hydrophobic Domain extending through the membrane and
3) An intracellular domain which often transmits a signal.

16. Archana Das
Ligand-gated ion channels are ion
channels that can open in response
to the binding of a ligand. To form a
channel, this type of cell-surface
receptor has a membrane-spanning
region with a hydrophilic (water-
loving) channel through the middle
of it. The channel lets ions to cross
the membrane without having to
touch the hydrophobic core of
the phospholipid bilayer.
Ligand Gated Ion Channels

17. Archana Das
G Protein Coupled Receptors
G protein-coupled receptors (GPCRs) are a large family of cell surface receptors
that share a common structure and method of signaling. GPCRs are diverse and
bind many different types of ligands.
G proteins come in different types, but they all
bind the nucleotide guanosine triphosphate
(GTP), which they can break down to form GDP.
One G protein attached to GTP is active while
another G protein that’s bound to GDP is
inactive. The G proteins that associate with
GPCRs are a type made up of three subunits,
known as heterotrimeric G proteins. When
they’re attached to an inactive receptor, they are
in the inactive form.

18. Receptor Tyrosine Kinases
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Enzyme-linked receptors are cell-surface
receptors with intracellular domains that
are associated with an enzyme. The
intracellular domain of the receptor
actually is an enzyme that can catalyse a
reaction. Other enzyme-linked receptors
have an intracellular domain that interacts
with an enzyme
Receptor tyrosine kinases (RTKs) are a
class of enzyme-linked receptors found in
humans and many other species.
A kinase is just a name for an enzyme that
transfers phosphate groups to a protein or
other target, and a receptor tyrosine
kinase transfers phosphate groups
specifically to the amino acid tyrosine.

19. Signal Transduction Pathways
Archana Das
The chain of reaction which transmits signals from the cell surface to an
intracellular target is called Signal Transduction Pathway
There are 6 different Signal Transduction Pathways. They are :
1. cAMP Pathway (Second Messenger)
2. cGMP Pathway
3. Calcium Ion (Ca++) Pathway
4. Phospholipid Pathway
5. Calmodulin Pathway
6. MAP Kinase Pathway

20. Archana Das
cAMP Pathway
When a Hormone or some
other Ligand binds to the outer
receptor of a cell as the first
messenger, cAMP is released
into the cell interior as the
Second Messenger and then it
activates a variety of other
cellular activities.
Function of cAMP Pathway
1. cAMP stimulates the glucose metabolism
by activating Protein Kinase.
2. Binding of Ligand to the outer surface of
Liver cell results in a change hormone
receptor conformation.
3. It stimulates the transmission of impulse
across the plama membrane to activate a
protein Adenyl cyclase.
4. Activated adenyl cyclase now converts
ATP into cAMP which quickly diffuses to
cytoplasm.
5. In the cytoplasm cAMP binds to Protein
Kinase A and prevents conversion of
glucose to glycogen.

21. Archana Das
cGMP Pathway
In animal cells cGMP
is formed from GTP.
This cGMP regulates
ion channels and its
action is regulated by
activation of cGMP
Dependant Protien
Kinases.
For example, in the
eyes of animals cGMP
serves as second
messenger during the
conversion of visual
signals of light to
nerve impulse.
Similarly, the Rhodopsin
present in the Rod cells
of retina is a G-Protein
Linked Receptor and it
brings conformational
changes introduced by
light in the receptor cells
of retina. This activates
G-Protein Transducing to
decrease the intercellular
level of cGMP. As a
result, light signals from
the retina quickly
changes to nerve impuse
and run along the optic
nerve.

22. Archana Das
Calcium Ion Pathway
Ca++ ions play important role as cellular and intracellular messengers as they can diffuse
into cytoplasm and bind to various target molecules. Ca++ ions play vital role in some
cellular activities like Cell division, Cell Secretion, Endocytosis, Synaptic transmission,
Cell movement and Fertilization.
Calcium signaling is the use of calcium
ions (Ca2+) to communicate and drive
intercellular processes often as a step
in signal transduction. Ca2+ is important
for cellular signalling, as once it enters
the cytosol of the cytoplasm it
exerts allosteric regulatory effects on
many enzymes and proteins. Ca2+ can act
in signal transduction resulting from
activation of ion channels or as a second
messenger caused by indirect signal
transduction pathways such as G protein-
coupled receptors

23. Archana Das
Phospholipid Pathway
Phospholipid signaling, broadly defined, refers to
any biological signaling event involving
a lipid messenger that binds a protein target, such
as a receptor, kinase or phosphatase, which in turn
mediate the effects of these lipids on specific
cellular responses. Lipid signaling is thought to be
qualitatively different from other classical signaling
paradigms because lipids can freely diffuse
through membranes .
One consequence of this is that lipid messengers
cannot be stored in vesicles prior to release and so
are often biosynthesized "on demand" at their
intended site of action. As such, many lipid
signaling molecules cannot circulate freely in
solution but, rather, exist bound to special carrier
proteins in serum.

24. Archana Das
Calmodulin Pathway
Calmodulin or CaM, is a polypeptide that is
ubiquitous in all eukaryotic cells. This protein is
known as calmodulin because it is a calcium-
modulated protein that plays a vital role in the
process of calcium signal transduction. Calcium
signal transduction is the process through which the
interactions between calcium ions and numerous
proteins mediate communication between cells.
calmodulin’s function, therefore, is necessary in all
eukaryotic cells, and some of the tasks that it helps
to accomplish are nerve signaling, skeletal muscle
movement, and memory. By sensing calcium ions in
the environment, calmodulin activates and
subsequently acts as an intermediate, initiating the
binding of important proteins such as kinases,
assisting our cells in basic and sophisticated
function
Structure of Calmodulin

25. Archana Das
Calmodulin (CaM) or calcium-
modulated protein is a
multifunctional intermediate
calcium-binding messenger
protein expressed in all eukaryotic
cells. It is an intracellular target of
the secondary messenger Ca2+,
and the binding of Ca2+ is required
for the activation of calmodulin.
Once bound to Ca2+, calmodulin
acts as part of a calcium signal
transduction pathway by
modifying its interactions with
various target proteins such
as kinases or phosphatases.

26. Archana Das
MAP Kinase Pathway
The MAP-K pathway is a chain of proteins in the cell that communicates a
signal from a receptor on the surface of the cell to the DNA in the nucleus
of the cell.
The signal starts when a signaling molecule binds to the receptor on the
cell surface and ends when the DNA in the nucleus expresses a protein
and produces some change in the cell, such as cell division. The pathway
includes many proteins, including MAP-K (Mitogen-Activated Protein
Kinases, extracellular signal-regulated kinases, which communicate by
adding phosphate groups to a neighboring protein which acts as an "on"
or "off" switch.
When one of the proteins in the pathway is mutated, it can become stuck
in the "on" or "off" position, which is a necessary step in the development
of many cancers. Components of the MAP-K pathway were discovered
when they were found in cancer cells. Drugs that reverse the "on" or "off"
switch are being investigated as cancer treatments

27. Archana Das
Archana Das, M.Sc.
Dept. of Zoology, Tangla College