Cell signaling Mechanism

1. MODES OF CELL TO CELL
SIGNALLING
Submitted by:
Lokesh Sv.M.R.P

2. CELL SIGNALLING
• Cell signaling is a process through which living cells interact with the cellular environment
and neighbouring cells by releasing and receiving hormones and other signaling molecules. as a
process, cell signaling refers to a vast network of communication between, and within, each cell of
our body.
• cell signaling enables coordination within multicellular organisms

3. Importance of Cell Signalling
 Maintenance of homeostasis
 Control of cell division and cell death
 Adaptation to environmental conditions
 Control of development and growth
 Release and production of hormones and other regulatory molecules, Response
elicited between organisms- including establishment of pathogenesis, activation
of defenses, establishment of symbiosis etc.

4. Process involved in cell
signalling
 Biosynthesis and release of the signal
 Transport of signal to target cell
 Transduction in target cell
 Alteration of cell growth and metabolism pertaining to response.
 Termination of signal

5. Categories of Signalling
Paracrine or Local Signalling
Neuronal signaling :special case of paracrine
Endocrine or Long distant signaling
Autocrine or Selfsignalling
Juxtacrine or Contact-dependent signalling

6. Signaling Molecules
• Ligand is an ion, molecule, or functional group that binds to another
chemical entity to form a larger complex
• Produced by signaling cells and the subsequent binding to receptors in
target cells, ligands act as chemical signals that travel to the target
cells to coordinate responses. The types of molecules that serve as
ligands are incredibly varied and range from small proteins to small
ions like calcium (Ca2+).

7. Small Hydrophobic Ligands
• Small hydrophobic ligands can directly diffuse
through the plasma membrane and interact with
internal receptors. Important members of this class of
ligands are the steroid hormones. Steroids are lipids
that have a hydrocarbon skeleton with four fused
rings; different steroids have different functional
groups attached to the carbon skeleton. Steroid
hormones include the female sex hormone, estradiol,
which is a type of estrogen; the male sex hormone,
testosterone; and cholesterol, which is an important
structural component of biological membranes and a
precursor of steriod hormones. Other hydrophobic
hormones include thyroid hormones and vitamin D.
In order to be soluble in blood, hydrophobic ligands
must bind to carrier proteins while they are being
transported through the bloodstream.

8. Water-Soluble Ligands
• Water-soluble ligands are polar and, therefore, cannot pass through the
plasma membrane unaided; sometimes, they are too large to pass
through the membrane at all. Instead, most water-soluble ligands bind
to the extracellular domain of cell-surface receptors. Cell-surface
receptors include: ion-channel, G-protein, and enzyme-linked protein
receptors. The binding of these ligands to these receptors results in a
series of cellular changes. These water soluble ligands are quite
diverse and include small molecules, peptides, and proteins.

9. Other Ligands
• Nitric oxide (NO) is a gas that also acts as a ligand. It is able to diffuse
directly across the plasma membrane; one of its roles is to interact
with receptors in smooth muscle and induce relaxation of the tissue.
NO has a very short half-life; therefore, it only functions over short
distances. Nitroglycerin, a treatment for heart disease, acts by
triggering the release of NO, which causes blood vessels to dilate
(expand), thus restoring blood flow to the heart.

10. Paracrine or Local Signalling
Signaling molecules are released from paracrine cells and diffuse locally through the extracellular fluid,
targeting cells that are nearby, thus acting as local mediators . Many of the cells that are involved in
inflammation during infection, or that regulate cell proliferation utilize this type of signaling.
For example cancer cells sometimes enhance their own survival or proliferation in this way. Examples of
signaling molecules that often function in a paracrine manner include transforming growth factor-β (TGF-β)
and fibroblast growth factors (FGFs).

11. Neuronal signaling :special case of paracrine
• Nerve cells (neurons) are specialized cells with a unique structure that can send signals
very quickly, over long distances and to specific target cells. A signal is detected by
receptors present on dendrites and then carried along the axon to a presynaptic terminal.
When the signal reaches the presynaptic terminal, vesicles containing signaling
molecules (neurotransmitters) fuse with the membrane, releasing the contents into the
synaptic space . These neurotransmitters are detected by receptors on the postsynaptic
membrane i.e. the cell membrane of the target cell, which may be another neuron or an
effector cell.
Examples of neurotransmitters include acetylcholine, serotonin and histamine

12. Endocrine or Long distant signaling
• This is the most common type of cell signaling and involves sending a signal throughout the whole body by
secreting hormones into the bloodstream of animals or the sap in plants . The cells that produce hormones in
animals are called endocrine cells. For example, the pancreas is an endocrine gland and produces the hormone
insulin, which regulates the uptake of glucose in cells all over the body.
• Examples of hormones that function in
• an endocrine manner include testosterone, progesterone and gonadotropins.

13. Autocrine or Self signalling
• Autocrine signaling is important in
immune system and it also frequently
contributes to uncontrolled growth
of cancer cells. In the situation cancer
cells produce a factor to which they
respond, deriving their own
unregulated proliferation.

14. Juxtacrine or Contact-dependent signalling
• This does not involve the release of secreted
molecules and only occurs over short distances. The
cells make direct physical contact through signal
molecules found in the plasma membrane of the
signaling cells and receptor proteins present in the
plasma membrane of the target cell. This type of
signaling is extremely important during embryonic
development and cell-fate determination (when
similar cells that are close to each other specialize to
form a specific cell type). The Notch pathway
mediates juxtacrine signaling between adjacent cells
Notch receptors are single transmembrane proteins
and they bind to specific ligands on adjacent cells.
Ligand binding results in proteolytic cleavage of the
Notch receptor which releases an intracellular
domain that is translocated to the nucleus where it
regulates gene expression.

15. Receptors
• Receptors are ligands. There are two protein molecules in the target
cell or on its surface that bind types of receptors: internal receptors
and cell-surface receptors.
• Internal Receptors
• Cell surface receptors
1. Ion channel-linked receptors
2. G- protein linked receptors
3. Enzyme linked receptors
• Receptor Tyrosine Kinases

16. Internal Receptors
• Internal receptors, also known as intracellular or cytoplasmic receptors, are
found in the cytoplasm of the cell and respond to hydrophobic ligand
molecules that are able to travel across the plasma membrane. Once inside the
cell, many of these molecules bind to proteins that act as regulators of
mRNA synthesis to mediate gene expression. Gene expression is the cellular
process of transforming
• The information in a cell’s DNA into a sequence of amino acids that
ultimately forms a protein. When the ligand binds to the internal receptor, a
conformational change exposes a DNA-binding site on the protein. The
ligand-receptor complex moves into the nucleus, binds to specific regulatory
regions of the chromosomal DNA, and promotes the initiation of
transcription. Internal receptors can directly influence gene expression
without having to pass the signal on to other receptors or messengers.

17. Cell surface receptors
• Cell-surface receptors, also known as transmembrane
receptors, are cell surface, membrane-anchored, or integral
proteins that bind to external ligand molecules. This type of
receptor spans the plasma membrane and performs signal
transduction, converting an extracellular signal into an
intracellular signal. Ligands that interact with cell-surface
receptors do not have to enter the cell that theyaffect.
• Cell-surface receptors are also called cell- specific proteins
or markers because they are specific to individual cell types.

18. Cell surface receptors
Each cell-surface receptor has three main components: an external ligand-
binding domain (extracellular domain), a hydrophobic membrane-spanning
region, and an intracellular domain inside the cell. The size and extent of
each of these domains vary widely, depending on the type of receptor.
Cell-surface receptors are involved in most of the signaling in multicellular
• organisms. There are three general categories of cell-surface receptors: ion
• channel-linked receptors, G-protein-linked receptors, and enzyme-linked
receptors.

19. Ion channel-linked receptors
• Ion channel-linked receptors bind a ligand and open a channel through the
membrane that allows specific ions to pass through. To form a channel, this type
of cell-surface receptor has an extensive membrane-spanning region. In order to
interact with the phospholipid fatty acid tails that form the center of the
plasma membrane, many of the amino acids in the membrane- spanning region
are hydrophobic in nature.
• Conversely, the amino acids that line the insideof the channel are hydrophilic
to allow for the passage of water or ions. When a ligand binds to the
extracellular region of the channel, there is a conformational change in the
protein’s structure that allows ions such as sodium, calcium, magnesium, and
hydrogen to pass through.

20. G- protein linked receptors
G-protein-linked receptors bind a ligand and activate a membrane
protein called a G-protein. The activated G- protein then interacts with
either an ion channel or an enzyme in the membrane. All G-protein-
linked receptors have seven transmembrane domains, but each receptor
has its own specific extracellular domain and G-protein- binding site.
Cell signaling using G-protein-linked receptors occurs as a cyclic series
of events. Before the ligand binds, the inactive G-protein can bind to a
newly-revealed site on the receptor specific for its binding. Once the G-
protein binds to the receptor, the resultant shape change activates the G-
protein, which releases GDP and picks up GTP. The subunits of the G-
protein then split into the α subunit and the β subunit. One or both of
these G- protein fragments may be able to activate other proteins as a
result. Later, the GTP on the active αsubunit of the G-protein is
hydrolyzed to GDP and the β subunit is deactivated. The subunits
reassociate to form the inactive G-protein, and the cycle starts over.

21. Enzyme linked receptors
• Enzyme-linked receptors are cell-surface receptors with intracellular domains that are
associated with an enzyme. In some cases, the intracellular domain of the receptor itself is an
enzyme or the enzyme-linked receptor has an intracellular domain that interacts directly with an
enzyme. The enzyme-linked receptors normally have large extracellular and intracellular
domains, but the membrane-spanning region consists of a single alpha-helical region of the
peptide strand. When a ligand binds to the extracellular domain, a signal is transferred through
the membrane and activates the enzyme, which sets off a chain of events within the cell that
eventually leads to a response. An example of this type of enzyme-linked receptor is the tyrosine
kinase receptor. The tyrosine kinase receptor transfers phosphate groups to tyrosine molecules.
Signalling molecules bind to the extracellular domain of two nearby tyrosine kinase receptors,
which then dimerize.
• Phosphates are then added to tyrosine residues on the intracellular domain of the receptors
and can then transmit the signal to the next messenger within the cytoplasm.

22. Receptor Tyrosine Kinases
• Receptor Tyrosine Kinases (RTKs)are another class of receptors revealed to show unforeseen diversity in
their actions and mechanisms of activation. The general method of activation follows aligand binding to
the receptor tyrosine kinase, which allows their kinase domains to dimerize. This dimerization then invites
the phosphorylation of their tyrosine kinase domains that, in turn, allow intracellular proteins to bind
the phosphorylated sites and become “active.” Animportant
• function of receptor tyrosine kinases are their roles in mediating growth pathways (i.e.,Epidermal Growth
Factors, Fibroblast Growth Factors). Of course, the downside of having complex signaling networks lies in
the unforeseen ways in which any alteration can produce disease or unregulated growth –cancer.

23. Binding Initiates a Signaling Pathway
• After the ligand binds to the cell-surface receptor, the
activation of the receptor’s intracellular components
sets off a chain of events that is called a signaling
pathway or a signaling cascade. In a signaling
pathway, second messengers, enzymes, and activated
proteins interact with specific proteins, which are in
turn activated in a chain reaction that eventually leads
to a change in the cell’s environment. The events in
the cascade occur in a series, much like a current
flows in a river. Interactions that occur before a certain
point are defined as upstream events; events after that
point are called downstream events.

24. • Signaling pathways can get very complicated very quickly because most cellular
proteins can affect different downstream events, depending on the conditions
within the cell. A single pathway can branch off toward different endpoints based
on the interplay between two or more signaling pathways. The same ligands are
often used to initiate different signals in different cell types. This variation in
response is due to differences in protein expression in different cell types. Another
complicating element is signal integration of the pathways in which signals from
two or more different cell-surface receptors merge to activate the same response in
the cell. This process can ensure that multiple external requirements are met
before a cell commits to a specific response.
• The effects of extracellular signals can also be amplified by enzymatic cascades.
At the initiation of the signal, a single ligand binds to a single receptor. However,
activation of a receptor-linked enzyme can activate many copies of a component
of the signaling cascade, which amplifies the signal.

25. Methods of Intracellular Signalling
• Signaling pathway induction activates a sequence of enzymatic modifications that are
recognized in turn by the next component downstream.
• The induction of a signaling pathway depends on the modification of a cellular
component by an enzyme. There are numerous enzymatic modifications that can occur
which are recognized in turn by the next component downstream.
• One of the most common chemical modifications that occurs in signaling pathways is
the addition of a phosphate group (PO4
–3) to a molecule such as a protein in a process
called phosphorylation. The phosphate can be added to a nucleotide such as GMP to
form GDP or GTP. Phosphates are also often added to serine, threonine, and tyrosine
residues of proteins where they replace the hydroxyl group of the amino acid. The
transfer of the phosphate is catalyzed by an enzyme called a kinase. Various kinases
are named for the substrate they phosphorylate. Phosphorylation of serine and
threonine residues often activates enzymes. Phosphorylation of tyrosine residues can
either affect the activity of an enzyme or create a binding site that interacts with
downstream components in the signaling cascade. Phosphorylation may activate or
inactivate enzymes; the reversal of phosphorylation, dephosphorylation by a
phosphatase, will reverse the effect.

26. • The activation of second messengers is also a common event after the
induction of a signaling pathway. They are small molecules that propagate a
signal after it has been initiated by the binding of the signaling molecule to
the receptor. These molecules help to spread a signal through the cytoplasm
by altering the behavior of certain cellular proteins.
• Calcium ion is a widely-used second messenger. The free concentration of
calcium ions (Ca2+) within a cell is very low because ion pumps in the plasma
membrane continuously use adenosine-5′-triphosphate ( ATP ) to remove it.
For signaling purposes, Ca2+ is stored in cytoplasmic vesicles, such as the
endoplasmic reticulum, or accessed from outside the cell. When signaling
occurs, ligand-gated calcium ion channels allow the higher levels of Ca2+ that
are present outside the cell (or in intracellular storage compartments) to flow
into the cytoplasm, which raises the concentration of cytoplasmic Ca2+. The
response to the increase in Ca2+ varies, depending on the cell type involved.
For example, in the β-cells of the pancreas, Ca2+ signaling leads to the release
of insulin, whereas in muscle cells, an increase in Ca2+ leads to muscle
contractions.
• Another second messenger utilized in many different cell types is cyclic AMP
(cAMP). Cyclic AMP is synthesized by the enzyme adenylyl cyclase from
ATP. The main role of cAMP in cells is to bind to and activate an enzyme
called cAMP-dependent kinase (A-kinase). A-kinase regulates many vital
metabolic pathways. It phosphorylates serine and threonine residues of its
target proteins, activating them in the process. A-kinase is found in many
different types of cells; the target proteins in each kind of cell are different.
Differences give rise to the variation of the responses to cAMP in different
cells.

27. • Present in small concentrations in the plasma membrane, inositol
phospholipids are lipids that can also be converted into second
messengers. Because these molecules are membrane components, they
are located near membrane-bound receptors and can easily interact
with them. Phosphatidylinositol (PI) is the main phospholipid that
plays a role in cellular signaling. Enzymes known as kinases
phosphorylate PI to form PI-phosphate (PIP) and PI-bisphosphate
(PIP2).

28. Termination of the Signal Cascade
• Signal cascades convey signals to the cell through the
phosphorylation of molecules by kinases.
Ligand binding to the receptor allows for signal
transduction through the cell. The chain of events that
conveys the signal through the cell is called a signaling
pathway or cascade. Signaling pathways are often very
complex because of the interplay between different
proteins. A major component of cell signaling cascades is
the phosphorylation of molecules by enzymes known as
kinases. Phosphorylation adds a phosphate group to serine,
threonine, and tyrosine residues in a protein, changing
their shapes, and activating or inactivating the protein.

29. • The aberrant signaling often seen in tumor cells is proof that the termination of a
signal at the appropriate time can be just as important as the initiation of a signal.
One method of terminating or stopping a specific signal is to degrade or remove
the ligand so that it can no longer access its receptor. One reason that hydrophobic
hormones like estrogen and testosterone trigger long-lasting events is because they
bind carrier proteins. These proteins allow the insoluble molecules to be soluble in
blood, but they also protect the hormones from degradation by circulating
enzymes.
• Inside the cell, many different enzymes reverse the cellular modifications that
result from signaling cascades. For example, phosphatases are enzymes that
remove the phosphate group attached to proteins by kinases in a process called
dephosphorylation. Cyclic AMP (cAMP) is degraded into AMP by
phosphodiesterase, and the release of calcium stores is reversed by the Ca2+ pumps
that are located in the external and internal membranes of the cell.

30. Reference
• https://www.khanacademy.org/science/ap-biology/cell-
communication-and-cell-cycle/cell-communication/a/introduction-to-
cell-signaling
• https://bio.libretexts.org/Bookshelves/Introductory_and_General_Bi
ology/Book%3A_General_Biology_(Boundless)/9%3A_Cell_Communi
cation/9.1%3A_Signaling_Molecules_and_Cellular_Receptors/9.1C%3
A_Types_of_Receptors
• https://courses.lumenlearning.com/boundless-
biology/chapter/signaling-molecules-and-cellular-receptors/

31. THANK YOU