CELL

SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

10/14/2023
CONTENT
1 2 3 4 5 6 7 8
Signal Receptors Propagation of the Binding Initiates a Methods of A Single Cell May Protein Cytosolic
Transduction Signal Signaling Pathway Intracellular Require Hundreds Phosphatases Turn Concentration Of
Signaling Of Different Off Signal- Ca2+ can Be
Protein Kinases transduction Altered
Pathways

9/3/20XX Presentation Title 2

LEARNING OBJECTIVES

1 2 3
Explain how the Recognize the role of Evaluate the role of
binding of a ligand phosphorylation in the second messengers in
initiates signal transmission of signal transmission
transduction throughout intracellular signals
a cell

9/3/20XX Presentation Title 3

SIGNAL-TRANSDUCTION
PATHWAYS
 CELL
SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT
Transduction is when the external signal is detected by
the cell and converted to an internal change. Typically,
the receptors are transmembrane
PREPARED proteins
BY FARHANA M.and span
SARIP BIO 281
the cell membrane.
SIGNAL TRANSDUCTION

Process by which a chemical or physical signal is transmitted

through a cell as a series of molecular events. Most commonly,

CELL
protein phosphorylation is catalyzed by protein kinases,
ultimately resulting in a cellular response. Proteins responsible
for detecting stimuli are generally termed receptors, although in

SIGNALING
some cases the term sensor is used. The changes elicited by
ligand binding (or signal sensing) in a receptor give rise to a
biochemical cascade, which is a chain of biochemical events
known as a signaling pathway.
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

STIMULI
The basis for signal transduction is the transformation of a
certain stimulus into a biochemical signal.
The nature of such stimuli can vary widely, ranging from

CELL
extracellular cues, such as the presence of EGF, to
intracellular events.
• Signals that reach the central nervous system are

SIGNALING
classified as senses, transmitted from neuron to neuron
in a process called synaptic transmission.

A CONTINUATION REPORT TO MS. BARAGONA’S

REPORT

PREPARED BY FARHANA M. SARIP BIO 281

Ligands

The binding of a signaling molecule with a receptor causes a change

in the conformation of the receptor, known as receptor activation.

CELL
Most ligands are soluble molecules from
the extracellular medium which bind to
cell surface receptors. These include

SIGNALING
growth factors, cytokines and
neurotransmitters.
A growth factor is a naturally occurring
substance capable of stimulating
A CONTINUATION REPORT TO MS. BARAGONA’S
cell proliferation, wound healing, and
REPORT
occasionally cellular differentiation.
Usually it is a secreted protein or a
steroid hormone. PREPARED BY FARHANA 3D Medical animation
M. SARIP BIO 281still showing signal
transduction.
Cytokines are a broad and loose category of small
proteins important in cell signaling. Due to their size,
cytokines cannot cross the lipid bilayer of cells to enter
the cytoplasm and therefore typically exert their functions
by interacting with specific cytokine receptors on the target

CELL
cell surface.

Cytokines have been shown to be involved in autocrine,

SIGNALING
paracrine and endocrine signaling as
immunomodulating agents.

Cytokines include chemokines, interferons,

A CONTINUATION REPORT TO MS. BARAGONA’S
interleukins, lymphokines, and tumour
REPORT
necrosis factors, but generally not hormones
or growth factors. 3D medical animation still showing
PREPARED BY FARHANA M. SARIP
secretion BIO 281
of cytokines
Mechanical Forces

Mechanotransduction is any of various

mechanisms by which cells convert
mechanical stimulus into electrochemical activity.

CELL
This form of sensory transduction is responsible for a
number of senses and physiological processes in the

SIGNALING
body, including proprioception, touch,balance, and
hearing.

A CONTINUATION REPORT TO MS. BARAGONA’S

REPORT

PREPARED BY FARHANA M. SARIP BIO 281

Osmolarity

An osmoreceptor is a sensory receptor primarily found in

the hypothalamus of most homeothermic organisms that
detects changes in osmotic pressure.

CELL
Cellular and systemic control of osmotic pressure (the
difference in osmolarity between the cytosol and the

SIGNALING
extracellular medium) is critical for homeostasis.

Cells can detect osmotic stimuli: as changes in

macromolecular crowding, ionic
A CONTINUATION strength,
REPORT and changes in
TO MS. BARAGONA’S
the properties of the plasma membrane or cytoskeleton
REPORT
(the latter being a form of mechanotransduction)
PREPARED BY FARHANA M. SARIP BIO 281
Temperature

The sensing of temperature in cells is known as thermoception and

is primarily mediated by transient receptor potential channels.

Light CELL
SIGNALING
The sensing of temperature in cells is known as thermoception and
is primarily mediated by transient receptor potential channels.

A CONTINUATION REPORT TO MS. BARAGONA’S

REPORT

PREPARED BY FARHANA M. SARIP BIO 281

RECEPTORS

Extracellular receptors are

integral transmembrane proteins and make up

CELL
most receptors. They span the
plasma membrane of the cell, with one part of
the receptor on the outside of the cell and the
other on the inside.

SIGNALING • Ligand-receptor binding induces a

change in the conformation of the
insideTO
A CONTINUATION REPORT part
MS.of the receptor, a process
BARAGONA’S
REPORT sometimes called "receptor activation"

PREPARED BY FARHANA M. SARIP BIO 281

RECEPTORS

G protein–coupled receptors (GPCRs)

Signal transduction by a GPCR begins with an inactive G protein

CELL
coupled to the receptor; the G protein exists as a heterotrimer
consisting of Gα, Gβ, and Gγ subunits (conserved signal
transduction mechanism in eukaryotes).

SIGNALING
• once the GPCR recognizes a ligand, the conformation of the receptor
changes to activate the G protein, causing Gα to bind a molecule of
GTP and dissociate from the other two G-protein subunits.
A CONTINUATION REPORT TO MS. BARAGONA’S
• dissociation exposes sites on the subunits that can interact with other
REPORT
molecules. The activated G protein subunits detach from the receptor
and initiate signaling from many downstream effector proteins
PREPARED BY FARHANA M. SARIP BIO 281
• the latter permitting the release of second messenger molecules
 G PROTEIN-COUPLED RECEPTORS
In the case of G protein-coupled receptors, the conformation
change exposes a binding site for a G-protein. The G-protein

CELL
(named for the GDP and GTP molecules that bind to it) is
bound to the inner membrane of the cell and consists of
three subunits: alpha, beta and gamma. The G-protein is
known as the “transducer”.

SIGNALING
A prime example of GPCRs in physiology is their well-
known involvement in the neurohumoral regulation of heart
contractility. Upon sympathetic activation, epinephrine and
norepinephrine Abind to β-adrenergic
CONTINUATION receptors
REPORT (βARs) on
TO MS. BARAGONA’S
the surface of REPORT
cardiomyocytes, where they exert positive
inotropic and chronotropic effects.
PREPARED BY FARHANA M. SARIP BIO 281
 CELL
SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

RECEPTORS

Tyrosine, Ser/Thr And Histidine-specific Protein Kinases

Receptor tyrosine kinases (RTKs) are transmembrane proteins with

CELL
an intracellular kinase domain and an extracellular domain that
binds ligands.

To perform signal transduction, RTKs need to form dimers in the

SIGNALING
plasma membrane; the dimer is stabilized by ligands binding to the receptor.

The interaction between the cytoplasmic domains stimulates the auto

phosphorylation of tyrosine residues within the intracellular kinase domains
A CONTINUATION REPORT TO MS. BARAGONA’S
of the RTKs, causing conformational changes.
REPORT

Subsequent to this, the receptors' kinase domains are activated, initiating

phosphorylation signalingPREPARED
cascades of downstream
BY FARHANA cytoplasmic
M. SARIP molecules
BIO 281
that facilitate various cellular processes such as cell differentiation and
metabolism.
RECEPTORS
As is the case with GPCRs, proteins that bind GTP play a major
role in signal transduction from the activated RTK into the cell. In
this case, the G proteins are members of the Ras, Rho, and Raf

CELL
families, referred to collectively as small G proteins. They act as
molecular switches usually tethered to membranes by isoprenyl
groups linked to their carboxyl ends.

SIGNALING
Upon activation, they assign proteins to specific membrane
subdomains where they participate in signaling. Activated RTKs in
turn activate small G proteins that activate
A CONTINUATION
guanine nucleotide exchange REPORT TO MS.
factors suchBARAGONA’S
as SOS1.
REPORT

Once activated, these exchange factors can activate more small G

proteins, thus amplifying the receptor's
PREPARED initial signal.
BY FARHANA M.The mutation
SARIP of
BIO 281
certain RTK genes, as with that of GPCRs, can result in the
expression of receptors that exist in a constitutively activated state;
such mutated genes may act as oncogenes.
RECEPTORS

Integrins
Produced by a wide variety of cells; they play a role in cell

CELL
attachment to other cells and the extracellular matrix and in the
transduction of signals from extracellular matrix components

• Ligand binding to the extracellular domain of

SIGNALING
integrins changes the protein's conformation,
clustering it at the cell membrane to initiate
signal transduction.
A CONTINUATION REPORT TO MS. BARAGONA’S
• IntegrinsREPORT
lack kinase activity; hence, integrin-
mediated signal transduction is achieved
through a variety of intracellular protein
PREPARED BY FARHANA M. SARIP BIO 281
kinases and adaptor molecules, the main
coordinator being integrin-linked kinase.
RECEPTORS

Toll-like receptors
When activated, toll-like receptors (TLRs) take adapter molecules
within the cytoplasm of cells in order to propagate a signal.

CELL
Four adaptor molecules: Myd88, TIRAP,
TRIF, and TRAM. These adapters activate

SIGNALING
other intracellular molecules such as IRAK1,
IRAK4, TBK1, and IKKi that amplify the
signal, eventually leading to the induction or
suppression of genes that cause certain
A CONTINUATION REPORT TO MS. BARAGONA’S
responses. REPORT

PREPARED BY FARHANA M. SARIP BIO 281

RECEPTORS

Ligand-gated ion channels

A ligand-gated ion channel, upon binding with a ligand, changes
conformation to open a channel in the cell membrane through

CELL
which ions relaying signals can pass.

SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

RECEPTORS
Intracellular receptors
Intracellular receptors, such as nuclear receptors and
cytoplasmic receptors, are soluble proteins localized within their

CELL
respective areas.
To initiate signal transduction, the ligand
must pass through the plasma membrane

SIGNALING
by passive diffusion. On binding with the
receptor, the ligands pass through the
nuclear membrane into the nucleus,
altering gene expression.
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT receptors attach to the DNA at
Activated nuclear
receptor-specific hormone-responsive element (HRE)
sequences, located in the promoter
PREPARED BYregion of theM.
FARHANA genes
SARIP BIO 281
activated by the hormone-receptor complex. Due to
their enabling gene transcription, they are alternatively
called inductors of gene expression.
Recall:
What Kind of Signals Do Cells Receive?
In multicellular organisms, growth factors, hormones, neurotransmitters, and
extracellular matrix components are some of the many types of chemical

CELL
signals cells use.

Neurotransmitters are a class of short-range signaling molecules that travel

across the tiny spaces between adjacent neurons or between neurons and

SIGNALING
muscle cells.

How Do Cells Recognize Signals?

A CONTINUATION REPORT TO MS. BARAGONA’S
Cells have proteins called receptors that bind to signaling molecules and
REPORT
initiate a physiological response. Different receptors are specific for different
molecules.
Membrane receptors fall intoPREPARED
three majorBY FARHANA
classes: M. SARIP BIO 281
G-protein-coupled
receptors, ion channel receptors, and enzyme-linked receptors.
Recall: In chemical signaling, a cell may
target itself (autocrine signaling), a
cell connected by gap junctions, a
nearby cell (paracrine signaling),
or a distant cell (endocrine
signaling).

CELL
SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

Recall:

CELL
SIGNALINGAn example of ion channel activation

acetylcholine molecules (green)

A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT
acetylcholine molecules (blue)
ions (red)
PREPARED BY FARHANA M. SARIP BIO 281
Recall:
The binding of adrenaline to an adrenergic
receptor initiates a cascade of reactions inside
the cell. The signal transduction cascade begins

CELL
when adenylyl cyclase, a membrane- bound
enzyme, is activated by G-protein molecules
associated with the adrenergic receptor.
Adenylyl cyclase creates multiple cyclic AMP

SIGNALING
molecules, which fan out and activate protein
kinases (PKA, in this example). Protein
kinases can enter the nucleus and affect
transcription. A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

Signal Transduction Cascade
involving cyclic AMP
 Propagation of the Signal
Once a ligand binds to a receptor, the signal is transmitted through the
membrane and into the cytoplasm. Continuation of a signal in this
manner is called signal transduction. Signal transduction only occurs

CELL
with cell-surface receptors because internal receptors are able to interact
directly with DNA in the nucleus to initiate protein synthesis.

SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M.transduction

Signal SARIP BIOpathways
281
regulate cell communication in a
wide variety of ways, including
metabolism, cell division, death,
differentiation, and movement.
 ligand binds an ion channel receptor

CELL
SIGNALING
• binding of the ligand causes dimerization of the receptor;
two receptors bind to each
A CONTINUATION other
REPORT TOto form
MS. a stable complex
BARAGONA’S
calledREPORT
a dimer
• a dimer is a chemical compound formed when two
PREPARED
molecules join together; BYtheir
enables FARHANA M. SARIP
intracellular domainsBIO 281
to come into close contact and activate each other.
 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

CELL
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

SIGNALING
that eventually leads to a change in the cell’s environment (Figure 1).
Events in the cascade:
• upstream events interactions that occur before a certain point
• downstream events REPORT
A CONTINUATION events after
TO MS.that point
BARAGONA’S
REPORT
Signal integration of the pathways; signals from two or more
different cell-surface receptors merge to activate the same response in
PREPARED BY FARHANA M. SARIP BIO 281
the cell.
• ensure that multiple external requirements are met before a
cell commits to a specific response
 CELL
SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT
Figure 1. The epidermal growth factor (EGF) receptor (EGFR) is a receptor tyrosine
kinase involved in the regulation of cell growth, wound healing, and tissue repair. When
PREPARED BY FARHANA M. SARIP BIO 281
EGF binds to the EGFR, a cascade of downstream events causes the cell to grow and
divide. If EGFR is activated at inappropriate times, uncontrolled cell growth (cancer)
may occur.
 CELL
SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

 Methods of Intracellular Signaling
1. Phosphorylation
2. Second Messengers

CELL
SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

 Methods of Intracellular Signaling
Phosphorylation
• addition of a phosphate group (PO4–3) to a molecule such as a protein

CELL
• phosphate can be added to a nucleotide such as GMP to form GDP or
GTP

SIGNALING
• often added to serine, threonine, and tyrosine residues of proteins,
where they replace the hydroxyl group of the amino acid (Figure 2)

A CONTINUATION REPORT TO MS. BARAGONA’S

REPORT

PREPARED BY FARHANA M. SARIP BIO 281

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

CELL
residues often activates enzymes.
Phosphorylation of tyrosine residues can either
affect the activity of an enzyme or create a

SIGNALING
binding site that interacts with downstream
components in the signaling cascade.
Phosphorylation may activate or inactivate
enzymes, and the reversal of phosphorylation,
dephosphorylation A by a phosphatase,
CONTINUATION will
REPORT TO MS. BARAGONA’S
reverse the effect. REPORT

PREPARED BY FARHANA
Figure 2.M.
In SARIP BIO 281
protein phosphorylation, a
phosphate group (PO4 ) is added to
−3

residues of the amino acids serine,

threonine, and tyrosine.
SECOND MESSENGERS
Second messengers are small molecules and ions that relay signals
received by cell-surface receptors to effector proteins.

CELL
Note:

First messengers are the signaling molecules (hormones,

neurotransmitters, and paracrine/autocrine agents) that

SIGNALING
reach the cell from the extracellular fluid and bind to their
specific receptors.

Second messengers
A CONTINUATION REPORT TO are the substances that enter the
MS. BARAGONA’S
REPORT
cytoplasm and act within the cell to trigger a response.In
essence, second messengers serve as chemical relays
from the plasma membrane
PREPARED BY FARHANA to theM.
cytoplasm,
SARIP BIOthus
281
carrying out intracellular signal transduction.
 Calcium
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.

CELL
• The release of calcium ions from the endoplasmic reticulum into the cytosol results
in its binding to signaling proteins that are then activated; it is then sequestered in
the smooth endoplasmic reticulum and the mitochondria.

SIGNALING
• Two combined receptor/ion channel proteins control the transport of calcium: the
InsP3-receptor that transports calcium upon interaction with inositol triphosphate
on its cytosolic side; and the ryanodine receptor similar to the InsP3 receptor but
A CONTINUATION REPORT TO MS. BARAGONA’S
having a feedback mechanism that releases more calcium upon binding with it.
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

Lipid Messengers
Lipophilic second messenger molecules are derived from lipids residing in
cellular membranes; enzymes stimulated by activated receptors activate
the lipids by modifying them.

CELL
SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

Nitric oxide
Nitric oxide (NO) acts as a second messenger because it is a free radical
that can diffuse through the plasma membrane and affect nearby cells.

It is synthesised from arginine and oxygen by the NO synthase and works

CELL
through activation of soluble guanylyl cyclase, which when activated
produces another second messenger, cGMP.

SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

Redox signaling
Other electronically activated species are also signal-transducing agents in
a process called redox signaling. Examples include superoxide, hydrogen
peroxide, carbon monoxide, and hydrogen sulfide.

CELL
SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

Cyclic AMP

Cyclic adenosine monophosphate (cAMP) is a second messenger used for

intracellular signal induction.

Synthesized by the enzyme adenylyl cyclase from ATP (Figure 3). The main

CELL
role of cAMP in cells is to bind to and activate an enzyme called cAMP-
dependent kinase (A-kinase).

SIGNALING
A-kinase regulates many vital metabolic pathways: It phosphorylates
serine and threonine residues of its target proteins, activating them in the
process.
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

 CELL
SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

Figure 3. This diagram shows the mechanism

PREPARED for the formation
BY FARHANA of cyclic
M. SARIP BIO AMP
281
(cAMP
 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).

CELL Diacylglycerol (DAG) and

Inositol Triphosphate (IP3)

SIGNALING
products of the cleavage of PIP2 serve as
second messengers

A CONTINUATION REPORT TO MS. BARAGONA’S

REPORT

The enzyme phospholipase C breaks down

PIP2 into IP3 and DAG, both of which serve as
PREPARED BY FARHANA M. SARIP BIO 281
second messengers.
 Hydrophobic molecules

Types Secondary • water-insoluble molecules such as diacylglycerol, and

Messenger phosphatidylinositols, which are membrane-associated

and diffuse from the plasma membrane into the

Molecules
intermembrane space where they can reach and regulate
membrane-associated effector proteins.

Hydrophilic molecules Gases

• water-soluble molecules, such as cAMP, cGMP, IP3, and Ca2+, • nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide
that are located within the cytosol (H2S) which can diffuse both through cytosol and across cellular
membranes

START
Mechanisms Secondary Messenger Molecules

CELL
SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
General
REPORT Schematic of Second Messenger
Mechanism

PREPARED BY FARHANA M. SARIP BIO 281

 IN SUMMARY:
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. Small molecules like nucleotides can also be phosphorylated. Second
messengers are small, non-protein molecules that are used to transmit a signal
within a cell. Some examples of second messengers are calcium ions (Ca2+),
cyclic AMP (cAMP), diacylglycerol (DAG), and inositol triphosphate (IP3).
 A Single Cell May Require Hundreds Of
Different Protein Kinases

CELL
Single cell requires thousands of kinases because kinases may
each phosphorylate a unique target, there are many different
pathways working at once inside.

SIGNALING
Protein kinases play a major role in cellular activation
processes. An important aspect of activation is the need to
provide stringent controls which
A CONTINUATION REPORTwill
TO allow for appropriate
MS. BARAGONA’S
enhancement and diminution of function. Protein kinase
REPORT
activities are regulated by interaction with other proteins.
PREPARED BY FARHANA M. SARIP BIO 281
 Protein Phosphatases Turn Off Signal-
transduction Pathways

CELL
Protein phosphatases are enzymes that can rapidly remove
phosphate groups from proteins (dephosphorylation) and thus

SIGNALING
inactivate protein kinases. Protein phosphatases are the "off
switch" in the signal transduction pathway.

A CONTINUATION REPORT TO MS. BARAGONA’S

REPORT

PREPARED BY FARHANA M. SARIP BIO 281

 Cytosolic Concentration Of Ca2+ can Be
Altered

Cytoplasmic concentration of Ca++ can be altered depending

CELL
on the signal molecules that induce responses in their target
cells. Increasing the cytosolic concentration of Ca2+ causes
many responses in animal cells, including muscle cell

SIGNALING
contraction, secretion of certain substance, and cell division.

Increased cytosolic calcium

A CONTINUATION REPORTconcentrations activate the
TO MS. BARAGONA’S
serine/threonine
REPORT phosphatase calcineurin, which
dephosphorylates cytosolic NFAT, which in turn traverses the
nuclear membrane.
PREPARED BY FARHANA M. SARIP BIO 281
 CELLULAR
RESPONSES TO
SIGNALS
CONTENT

1 2
What Is Cellular Response? Major Pathways

9/3/20XX Presentation Title 51

 What Is Cellular Response?

A cellular response is the response of a cell to

extracellular signals. Cells, particularly cells in

Primary
multicellular organisms, must be able to communicate
and coordinate responses to maintain homeostasis in
the body. Cellular communication is complicated.

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CELLULAR RESPONSES
Gene activations and metabolism alterations are examples of cellular
responses to extracellular stimulation that require signal transduction.

CELL
SIGNALING
A CONTINUATION REPORT TO MS. BARAGONA’S
REPORT

PREPARED BY FARHANA M. SARIP BIO 281

CELLULAR RESPONSES
Three basic signals determine cellular growth:
1. Stimulatory (growth factors)
• Transcription dependent response

CELL
For example, steroids act directly as transcription factor (gives
slow response, as transcription factor must bind DNA, which
needs to be transcribed. Produced mRNA needs to be translated,

SIGNALING
and the produced protein/peptide can undergo
posttranslational modification (PTM).

• Transcription independent response

For example, epidermal
A CONTINUATION growth
REPORT TOfactor (EGF) binds the
MS. BARAGONA’S
REPORT
epidermal growth factor receptor (EGFR), which causes
dimerization and autophosphorylation of the EGFR, which in turn
activates the intracellular
PREPARED signaling pathway. M. SARIP BIO 281
BY FARHANA
2. Inhibitory (cell-cell contact)
3. Permissive (cell-matrix interactions)
Major pathways

MAPK/ERK pathway

cAMP-dependent pathway
IP3/DAG pathway

Primary
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Major pathways

MAPK/ERK pathway
A pathway that couples intracellular responses to the binding
of growth factors to cell surface receptors. This pathway is
very complex and includes many protein components. In many

Primary
cell types, activation of this pathway promotes cell division,
and many forms of cancer are associated with aberrations in it.

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Major pathways

cAMP-dependent pathway
In humans, cAMP works by activating protein kinase A (PKA,
cAMP-dependent protein kinase) (see picture), and, thus,
further effects depend mainly on

Primary
cAMP-dependent protein kinase, which vary based on the type
of cell.

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Major pathways

IP3/DAG pathway
PLC cleaves the phospholipid
phosphatidylinositol 4,5-bisphosphate (PIP2), yielding
diacyl glycerol (DAG) and inositol 1,4,5-triphosphate (IP3).
Primary
DAG remains bound to the membrane, and IP3 is released as
a soluble structure into the cytosol.

goals
IP3 then diffuses through the cytosol to bind to IP3 receptors,
particular calcium channels in the endoplasmic reticulum
(ER). These channels are specific to calcium and allow the
passage of only calcium to move through. This causes the
Annualofrevenue
cytosolic concentration Calciumgrowth
to increase, causing a
cascade of intracellular changes and activity.
Gene expression, an example of a cellular response,
is the process of reading genes and creating protein
products. Not all genes are on all at once in any given cell,

Primary
and extracellular signals can cause changes that allow genes
to be turned on or off.

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LEARNING OBEJECTIVES

1 2 3
signal information is signal amplification is different types of cells
transduced into cellular accomplished in target may respond differently
responses in the cells to the same signal
cytoplasm and in the molecule
nucleus

9/3/20XX Presentation Title 60

 Signal Information Is Transduced Into Cellular
Responses In The Cytoplasm
signal converted into a cellular response during signal transduction

Primary
• A ligand binds to a receptor, leading indirectly to activation of
adenylyl cyclase, which converts ATP to cAMP. cAMP binds to
protein kinase A and activates it, allowing PKA to phosphorylate

goals
downstream factors to produce a cellular response.
• Receptors transmit information from the extracellular environment
to the inside of the cell by changing shape or by joining with
another protein once a specific ligand binds to it.
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 Signal Information Is Transduced Into Cellular
Responses In The Nucleus
Signal information is transduced into cellular responses in the
cytoplasm and in the nucleus with an initial signaling molecule, a

Primary
growth factor, triggers a phosphorylation cascade. Once
phosphorylated, the last kinase in the sequence enters the nucleus and
activates a gene-regulating protein, a transcription factor.
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Annual revenue growth
 Signal Amplification Is Accomplished
In Target Cells

Signal amplification is achieved by enzymatic action in a cell.

Primary
Enzymes can catalyze the production of several signalling
molecules in a short time when activated and this can amplify
the signal received at the cell surface several fold.
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Annual revenue growth
Different Types Of Cells May Respond Differently To The Same
Signal Molecule

Different cells have different patterns of carbohydrates on their

Primary
cell surfaces. Nuclear envelope proteins vary from cell type to
cell type, and this means that cells respond to signaling
molecules differently. Different types of cells possess different
proteins.
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Annual revenue growth
 Presenter name
Farhana M. Sarip

Email address

THANK sarip.fm15@s.msumain.edu.ph

YOU!

9/3/20XX Presentation Title 65