Cell Signaling

In order to respond to changes in their immediate environment, cells must be able to

receive and process signals that originate outside their borders. Individual cells often
receive many signals simultaneously, and they then integrate the information they
receive into a unified action plan. But cells aren't just targets. They also send out
messages to other cells both near and far.
What Kind of Signals Do Cells Receive?
Most cell signals are chemical in nature. For example, prokaryotic organisms have
sensors that detect nutrients and help them navigate toward food sources. In
multicellular organisms, growth factors, hormones, neurotransmitters, and
extracellular matrix components are some of the many types of chemical signals cells
use. These substances can exert their effects locally, or they might travel over long
distances. For instance, neurotransmitters are a class of short-range signaling
molecules that travel across the tiny spaces between adjacent neurons or between
neurons and muscle cells. Other signaling molecules must move much farther to reach
their targets. One example is follicle-stimulating hormone, which travels from the
mammalian brain to the ovary, where it triggers egg release.

Some cells also respond to mechanical stimuli. For example, sensory cells in the skin
respond to the pressure of touch, whereas similar cells in the ear react to the
movement of sound waves. In addition, specialized cells in the human vascular
system detect changes in blood pressure — information that the body uses to maintain
a consistent cardiac load.

1
 Fig.1 show type of chemical signals

How Do Cells Recognize Signals?

Cells have proteins called receptors that bind to signaling molecules and initiate a
physiological response. Different receptors are specific for different molecules.
Dopamine receptors bind dopamine, insulin receptors bind insulin, nerve growth
factor receptors bind nerve growth factor, and so on. In fact, there are hundreds of
receptor types found in cells, and varying cell types have different populations of
receptors. Receptors can also respond directly to light or pressure, which makes cells
sensitive to events in the atmosphere.

2
Receptors are generally transmembrane proteins, which bind to signaling molecules
outside the cell and subsequently transmit the signal through a sequence of molecular
switches to internal signaling pathways. Membrane receptors fall into three major
classes: G-protein-coupled receptors, ion channel receptors, and enzyme-linked
receptors. The names of these receptor classes refer to the mechanism by which the
receptors transform external signals into internal ones — via protein action, ion
channel opening, or enzyme activation, respectively. Because membrane receptors
interact with both extracellular signals and molecules within the cell, they permit
signaling molecules to affect cell function without actually entering the cell. This is
important because most signaling molecules are either too big or too charged to cross
a cell's plasma membrane Not all receptors exist on the exterior of the cell. Some exist
deep inside the cell, or even in the nucleus. These receptors typically bind to
molecules that can pass through the plasma membrane, such as gases like nitrous
oxide and steroid hormones like estrogen.

Fig.2 show steps of cell signalling

1- Reception: A signal molecule binds to a receptor protein, causing it to change

shape

The binding between a signal molecule (ligand) and receptor is highly specific

A conformational change in a receptor is often the initial transduction of the signal

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Most signal receptors are plasma membrane proteins

2- Transduction: Cascades of molecular interactions relay signals from receptors

to target molecules in the cell

Transduction usually involves multiple steps

Multistep pathways can amplify a signal: A few molecules can produce a large
cellular response

Multistep pathways provide more opportunities for coordination and regulation

Fig.3 modes of transduction

how Do Cells Respond to Signals?

Once a receptor protein receives a signal, it undergoes a conformational change,
which in turn launches a series of biochemical reactions within the cell. These
intracellular signaling pathways, also called signal transduction cascades, typically
amplify the message, producing multiple intracellular signals for every one receptor
that is bound.

Activation of receptors can trigger the synthesis of small molecules called second
messengers, which initiate and coordinate intracellular signaling pathways. For

4
example, cyclic AMP (cAMP) is a common second messenger involved in signal
transduction cascades. (In fact, it was the first second messenger ever discovered.)
cAMP is synthesized from ATP by the enzyme adenylyl cyclase, which resides in the
cell membrane. The activation of adenylyl cyclase can result in the manufacture of
hundreds or even thousands of cAMP molecules. These cAMP molecules activate the
enzyme protein kinase A (PKA), which then phosphorylates multiple protein
substrates by attaching phosphate groups to them. Each step in the cascade further
amplifies the initial signal, and the phosphorylation reactions mediate both short- and
long-term responses in the cell (Figure 2). How does cAMP stop signaling? It is
degraded by the enzyme phosphodiesterase.

Other examples of second messengers include diacylglycerol (DAG) and inositol

1,4,5-triphosphate (IP3), which are both produced by the enzyme phospholipase,
also a membrane protein. IP3 causes the release of Ca2+ — yet another second
messenger — from intracellular stores. Together, DAG and Ca2+ activate another
enzyme called protein kinase C (PKC).

how Do Signals Affect Cell Function?

Protein kinases such as PKA and PKC catalyze the transfer of phosphate groups from
ATP molecules to protein molecules. Within proteins, the amino acids serine,
threonine, and tyrosine are especially common sites for phosphorylation. These
phosphorylation reactions control the activity of many enzymes involved in
intracellular signaling pathways. Specifically, the addition of phosphate groups causes
a conformational change in the enzymes, which can either activate or inhibit the
enzyme activity. Then, when appropriate, protein phosphatases remove the phosphate
groups from the enzymes, thereby reversing the effect on enzymatic activity.

Phosphorylation allows for intricate control of protein function. Phosphate groups can
be added to multiple sites in a single protein, and a single protein may in turn be the
substrate for multiple kinases and phosphatases.

At any one time, a cell is receiving and responding to numerous signals, and multiple
signal transduction pathways are operating in its cytoplasm. Many points of
intersection exist among these pathways. For instance, a single second messenger or
protein kinase might play a role in more than one pathway. Through this network of
signaling pathways, the cell is constantly integrating all the information it receives
from its external environment.

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Fig.4 show mech. Of cell signalling

The Role of calcium ions in blood clotting

Cells may show an increase of cytosolic calcium because of because of the
appearance of a transmitter or other chemical in the extracellular medium.
The presence of the chemical is detected by integral membrane proteins, each one a
receptor that recognizes a particular chemical with high affinity. These receptors then
participate in a more general mechanism, the end result of which is the release of
calcium ions from the smooth endoplasmic reticulum into the cytosol. This
mechanism will be illustrated with the particular example of blood platelets. We will
then discuss how much of the mechanism is general to a wider range of cells.
Platelets are common in the blood. They are small fragments of cells and contain no
nucleus, but they do have a plasma membrane and some endoplasmic reticulum.
Blood platelets use the release of calcium from the endoplasmic reticulum as one step
in the mechanism of blood clotting.
If a blood vessel is cut, cytosol from damaged cells at the edge of the cut can leak into
the blood. The appearance of solutes that normally are found only inside cells is a sure
sign that damage has occurred. Adenosine diphosphate (ADP) is one such solute, and
it acts to stimulate platelets, causing them to begin a blood clot to help plug the
damaged vessel. The plasma membrane of the platelet contains a protein receptor that
binds ADP, that is, ADP is its ligand. When the ADP has bound, the receptor, which
is free to move in the plasma membrane, becomes a guanine nucleotide exchange
factor (for a trimeric G protein called Gq.
trimeric G proteins are GTPases that activate target proteins when they have GTP

6
bound, but turn themselves off by hydrolyzing the GTP to GDP. Trimeric G proteins
have a slight additional complication in that, as the name indicates, they are composed
of three subunits. The α subunit is homologous to the GTPases we have met before,
while the β and γ subunits dissociate from the α subunit when it has GTP bound and
only reassociate when the GTP has been hydrolyzed. GTP-loaded Gq activates the β
isoform of an enzyme called phosphoinositide phospholipase C, which we will call
phospholipase C or just PLC
). PLC specifically hydrolyzes phosphatidylinositol bisphosphate (PIP2 for short), a
phospholipid in the plasma membrane that has phosphorylated inositol as its polar
head group. Hydrolysis releases the IP3 to diffuse freely in the cytosol, leaving behind
the glycerol backbone with its attached fatty acids: this residual lipid is called
diacylglycerol, or DAG. As it diffuses through the cytosol, IP3 reaches the
endoplasmic reticulum and binds to the inositol trisphosphate-gated calcium channels.
The inositol trisphosphate-gated calcium channels open, and calcium ions pour out of
the endoplasmic reticulum into the cytosol.
The increase of calcium concentration causes the platelet to change shape and to
become very sticky, so platelets begin to clump together in a clot.
Phosphatidylinositol bisphosphate,Gq, PLCβ, and the inositol trisphosphate-gated
calcium channel are found in almost all eukaryotic cells, but the distribution of the
ADP receptor is more restricted. Only cells that express the ADP receptor will show
an increase of cytosolic calcium concentration in response to ADP. Other cells
respond to other chemicals.
Each produces a receptor specific for that chemical, which then activates Gq. Over
100 such receptors are known. We will meet two more in the next chapter.

Fig .5
The inositol trisphosphate-gated calcium channel receptor is a calcium-selective
channel in the membrane of the endoplasmic reticulum. An increase of cytosolic
calcium concentration in platelets makes them sticky, initiating blood clotting.

7
Fig.6
Relationship of hormones and cell signal transduction
Hormones Can Be Classified Based on Their Solubility and Receptor Location

Most hormones fall into three broad categories: (1) small lipophilic molecules that
diffuse across the plasma membrane and interact with intracellular receptors; and (2)
hydrophilic or (3) lipophilic molecules that bind to cell-surface receptors Recently,
nitric oxide, a gas, has been shown to be a key regulator controlling many cellular
responses.

Lipophilic Hormones with Intracellular Receptors

Many lipid-soluble hormones diffuse across the plasma membrane and interact with
receptors in the cytosol or nucleus. The resulting hormone-receptor complexes bind to
transcription-control regions in DNA thereby affecting expression of specific genes.
Hormones of this type include the steroids (e.g., cortisol, progesterone, estradiol, and
testosterone), thyroxine, and retinoic acid All steroids are synthesized from
cholesterol and have similar chemical skeletons. After crossing the plasma membrane,
steroid hormones interact with intracellular receptors, forming complexes that can
increase or decrease transcription of specific genes. These receptor-steroid complexes
also may affect the stability of specific mRNAs. Steroids are effective for hours or
days and often influence the growth and differentiation of specific tissues. For
example, estrogen and progesterone, the female sex hormones, stimulate the
production of egg-white hormones in chickens and cell proliferation in the hen
oviduct. In mammals, estrogens stimulate growth of the uterine wall in preparation for
embryo implantation. In insects and crustaceans, -ecdysone (which is chemically
related to steroids) triggers the differentiation and maturation of larvae; like estrogens,
it induces the expression of specific gene products.

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Thyroxine (tetraiodothyronine) and triiodothyronine the principal iodinated
compounds in the body are formed in the thyroid by intracellular proteolysis of the
iodinated protein thyroglobulin and immediately released into the blood.

These two thyroid hormones stimulate increased expression of many cytosolic

enzymes (e.g., liver hexokinase) that catalyze the catabolism of glucose, fats, and
proteins and of mitochondrial enzymes that catalyze oxidative phosphorylation.

Retinoids are polyisoprenoid lipids derived from retinol (vitamin A). They perform
multiple regulatory functions in diverse cellular processes. Retinoids regulate cellular
proliferation, differentiation, and death, and they have numerous clinical applications.
Their diverse effects reflect, at least in part, the multiplicity of retinoid derivatives, the
existence of two different classes of receptors that form heterodimers, and differences
in their cis-acting regulatory sites on DNA. During development retinoids act as local
mediators of cell-cell interaction. For instance, during the formation of motor neurons
in the chick, one class of motor neurons generates a retinoid signal which regulates
the number and type of neighboring motoneurons.

Water-Soluble Hormones with Cell-Surface Receptors

Because water-soluble signaling molecules cannot diffuse across the plasma

membrane, they all bind to cell-surface receptors. This large class of compounds is
composed of two groups: (1) peptide hormones, such as insulin, growth factors, and
glucagon, which range in size from a few amino acids to protein-size compounds, and
(2) small charged molecules, such as epinephrine and histamine that are derived from
amino acids and function as hormones and neurotransmitters.

Many water-soluble hormones induce a modification in the activity of one or more

enzymes already present in the target cell. In this case, the effects of the surface-

9
bound hormone usually are nearly immediate, but persist for a short period only.
These signals also can give rise to changes in gene expression that may persist for
hours or days. In yet other cases water-soluble signals may lead to irreversible
changes, such as cellular differentiation.

Lipophilic Hormones with Cell-Surface Receptors

The primary lipid-soluble hormones that bind to cell-surface receptors are the
prostaglandins. There are at least 16 different prostaglandins in nine different
chemical classes, designated PGA PGI. Prostaglandins are part of an even larger
family of 20 carbon containing hormones called eicosanoid hormones. In addition to
prostaglandins, they include prostacyclins, thromboxanes, and leukotrienes.
Eicosonoid hormones are synthesized from a common precursor, arachidonic acid.
Arachidonic acid is generated from phospholipids and diacylglycerol.

In both vertebrates and invertebrates, prostaglandins are synthesized and secreted

continuously by many types of cells and rapidly broken down by enzymes in body
fluids.

Many prostaglandins act as local mediators during paracrine and autocrine signaling
and are destroyed near the site of their synthesis. They modulate the responses of
other hormones and can have profound effects on many cellular processes. Certain
prostaglandins cause blood platelets to aggregate and adhere to the walls of blood
vessels. Because platelets play a key role in clotting blood and plugging leaks in
blood vessels, these prostaglandins can affect the course of vascular disease and
wound healing; aspirin inhibits their synthesis by acetylating (and thereby irreversibly
inhibiting) prostaglandin H2 synthase. Other prostaglandins initiate the contraction of
smooth muscle cells; they accumulate in the uterus at the time of childbirth and
appear to be important in inducing uterine contraction.

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Recent studies have shown that a family of plant steroids, called brassinosteroids,
regulates many aspects of development. These lipophilic compounds, like
prostaglandins, act through cell-surface receptors.

Cell-Surface Receptors Belong to Four Major Classes

The different types of cell-surface receptors that interact with water-soluble ligands
are schematically represented in Figure 4. Binding of ligand to some of these
receptors induces second-messenger formation, whereas ligand binding to others does
not. For convenience, we can sort these receptors into four classes:

 G protein coupled receptors Ligand binding activates a G protein, which in

turn activates or inhibits an enzyme that generates a specific second messenger
or modulates an ion channel, causing a change in membrane potential. The
receptors for epinephrine, serotonin, and glucagon are examples.
 Ion-channel receptors ligand binding changes the conformation of the receptor
so that specific ions flow through it; the resultant ion movements alter the
electric potential across the cell membrane. The acetylcholine receptor at the
nerve-muscle junction is an example.
 Tyrosine kinase linked receptors These receptors lack intrinsic catalytic
activity, but ligand binding stimulates formation of a dimeric receptor, which
then interacts with and activates one or more cytosolic protein-tyrosine
kinases. The receptors for many cytokines, the interferons, and human growth
factor are of this type. These tyrosine kinase linked receptors sometimes are
referred to as the cytokine-receptor superfamily.
 Receptors with intrinsic enzymatic activity Several types of receptors have
intrinsic catalytic activity, which is activated by binding of ligand. For
instance, some activated receptors catalyze conversion of GTP to cGMP;
others act as protein phosphatases, removing phosphate groups from
phosphotyrosine residues in substrate proteins, thereby modifying their
activity. The receptors for insulin and many growth factors are ligand-
triggered protein kinases; in most cases, the ligand binds as a dimer, leading to
dimerization of the receptor and activation of its kinase activity. These
receptors often referred to as receptor serine/threonine kinases or receptor
tyrosine kinases autophosphorylate residues in their own cytosolic domain
and also can phosphorylate various substrate proteins.

Effects of Many Hormones Are Mediated by Second Messengers

The binding of ligands to many cell-surface receptors leads to a short-lived increase

(or decrease) in the concentration of the intracellular signaling molecules termed
second messengers. These low-molecular-weight signaling molecules include 3 ,5 -
cyclic AMP (cAMP); 3 ,5 -cyclic GMP (cGMP); 1,2-diacylglycerol (DAG); inositol
1,4,5-trisphosphate (IP3); various inositol phospholipids (phosphoinositides); and Ca2+

The elevated intracellular concentration of one or more second messengers following

hormone binding triggers a rapid alteration in the activity of one or more enzymes or
nonenzymatic proteins. The metabolic functions controlled by hormone-induced
second messengers include uptake and utilization of glucose, storage and mobilization
of fat, and secretion of cellular products. These intracellular molecules also control

11
proliferation, differentiation, and survival of cells, in part by regulating the
transcription of specific genes. The mode of action of cAMP and other second
messengers is discussed in a later section. Removal (or degradation) of a ligand or
second messenger, or inactivation of the ligand-binding receptor, can terminate the
cellular response to an extracellular signal.

Other Conserved Proteins Function in Signal Transduction

In addition to cell-surface receptors and second messengers, several types of

conserved proteins function in signal transduction pathways stimulated by
extracellular signals. Here we introduce the three main classes of these intracellular
signaling proteins; their structures and functions are described in detail in later
sections.

GTPase Switch Proteins

A large group of GTP-binding proteins act as molecular switches in signal-

transduction pathways. These proteins are turned "on" when bound to GTP and turned
"off" when bound to GDP In the absence of a signal, the protein is bound to GDP.
Signals activate the release of GDP, and the subsequent binding to GTP over GDP is
favored by the higher concentrations of GTP in the cell. The intrinsic GTPase activity
of these GTP-binding proteins hydrolyzes the bound GTP to GDP and P i, thus
converting the active form back to the inactive form. The kinetics of hydrolysis
regulates the length of time the switch is "on."

There are two classes of GTPase switch proteins: trimeric G proteins, which as noted
already are directly coupled to certain receptors, and monomeric Ras and Ras-like
proteins. Both classes contain regions that promote the activity of specific effector
proteins by direct protein-protein interactions. These regions are in their active
conformation only when the switch protein is bound to GTP. G proteins are coupled
directly to activated receptors, whereas Ras is linked only indirectly via other
proteins. The two classes of GTPbinding proteins also are regulated in very different
ways.

Protein Kinases

Activation of all cell-surface receptors leads to changes in protein phosphorylation

through the activation of protein kinases In some cases kinases are part of the receptor
itself, and in others they are found in the cytosol or associated with the plasma
membrane. Animal cells contain two types of protein kinases: those directed toward
tyrosine and those directed toward either serine or threonine. The structures of the
catalytic core of both types are very similar. In general, protein kinases become active
in response to the stimulation of signaling pathways. The catalytic activities of
kinases are modulated by phosphorylation, by direct binding to other proteins, and by
changes in the levels of various second messengers. The activity of protein kinases is
opposed by the activity of protein phosphatases, which remove phosphate groups
from specific substrate proteins..

Adapter Proteins

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Many signal-transduction pathways contain large multiprotein signaling complexes,
which often are held together by adapter proteins Adapter proteins do not have
catalytic activity, nor do they directly activate effector proteins. Rather, they contain
different combinations of domains, which function as docking sites for other proteins.
For instance, different domains bind to phosphotyrosine residues (SH2 and PTB
domains), proline-rich sequences (SH3 and WW domains), phosphoinositides (PH
domains), and unique C-terminal sequences with a C-terminal hydrophobic residue
(PDZ domains). In some cases adapter proteins contain arrays of a single binding
domain or different combinations of domains. In addition, these binding domains can
be found alone or in various combinations in proteins containing catalytic domains.
These combinations provide enormous potential for complex interplay and cross-talk
between different signaling pathways.

Common Signaling Pathways Are Initiated by Different Receptors in a Class

In general, different members of a particular class of receptors transduce signals by

highly conserved pathways. Moreover, analogies are found in the signaling pathways
associated with different receptor classes. illustrates the main components of the key
signaling pathways downstream from G protein coupled receptors (GPCRs) and
receptor tyrosine kinases (RTKs), the two receptor classes that we consider in detail in
this chapter. Although a GTPase switch protein occurs in both types of pathways, its
position in the pathway relative to the receptor differs. Second messengers are critical
components of most GPCR pathways and some RTK pathways. Adapter proteins
function in all RTK pathways but not in the main GPCR pathways. Protein kinases,
however, play a key role in all signaling pathways; ultimately an activated protein
kinase phosphorylates one or more substrate proteins. The nature of the substrate
proteins, which include enzymes, microtubules, histones, and transcription factors,
plays an important role in determining the cellular response to a particular signal in a
particular cell.

The Synthesis, Release, and Degradation of Hormones Are Regulated

Because of their potent effects, hormones and neurotransmitters must be carefully

regulated. The release and degradation of some signaling compounds are regulated to
produce rapid, short-term effects; others to produce slower-acting but longer-lasting
effect In some cases, complex regulatory networks coordinate the levels of hormones
whose effects are interconnected.

Peptide Hormones and Catecholamines

Organisms must be able to respond instantly to many changes in their internal or
external environment. Such rapid responses are mediated primarily by peptide
hormones and the catecholamines epinephrine, norepinephrine, and dopamine The
cells that produce these signaling molecules store them in secretory vesicles just under
the plasma membrane. The supply of stored, preformed signaling molecules is
sufficient for 1 day in the case of peptide hormones and for several days in the case of

13
catecholamines. All peptide hormones, including insulin and adrenocorticotropic
hormone (ACTH), are synthesized as part of a longer propolypeptide, which is
cleaved by specific proteases to generate the active molecule just after it is transported
to a secretory vesicle

Stimulation of signaling cells causes immediate exocytosis of the stored peptide

hormone or catecholamine into the surrounding medium or the blood. Secreting cells
also are stimulated to synthesize the signaling molecule and replenish the cell's
supply. Released peptide hormones persist in the blood for only seconds or minutes
before being degraded by blood and tissue proteases. Released catecholamines are
rapidly inactivated by different enzymes or taken up by specific cells. The initial
actions of these signaling molecules on target cells (the activation or inhibition of
specific enzymes) also last only seconds or minutes. Thus the catecholamines and
some peptide hormones can mediate short responses that are terminated by their own
degradation.

Steroid Hormones
The pathways for synthesizing steroid hormones from cholesterol involve 10 or more
enzymes. Steroid-producing cells, like those in the adrenal cortex, store a small
supply of hormone precursor but none of the mature, active hormone. When
stimulated, the cells convert the precursor to the active hormone, which then diffuses
across the plasma membrane into the blood. Likewise, thyroglobulin, the iodinated
precursor of thyroxine is stored in thyroid follicles. When cells lining these follicles
are exposed to thyroid-stimulating hormone (TSH), they take up thyroglobulin;
controlled proteolysis of this glycoprotein by lysosomal enzymes yields thyroxine,
which is released into the blood.

Signal Amplification
Enzyme cascades amplify the cell’s response

At each step, the number of activated products is much greater than in the preceding
step

14
Fig.7 show signal amplification

Muscle Contraction uses Calcium as 2nd messenger

Fig .8 show transmition through synapsis

Termination of the Signal

Inactivation mechanisms are an essential aspect of cell signaling

When signal molecules leave the receptor, the receptor reverts to its inactive state

Apoptosis (programmed cell death)

Apoptosis is programmed or controlled cell suicide

A cell is chopped and packaged into vesicles that are digested by scavenger cells

Apoptosis prevents enzymes from leaking out of a dying cell and damaging
neighboring cells

Apoptotic Pathways and the Signals That Trigger Them

Caspases are the main proteases (enzymes that cut up proteins) that carry out
apoptosis

15
Apoptosis can be triggered by:

-An extracellular death-signaling ligand

-DNA damage in the nucleus

-Protein misfolding in the endoplasmic reticulum

Apoptosis evolved early in animal evolution and is essential for the development and
maintenance of all animals

Apoptosis may be involved in some diseases (for example, Parkinson’s and

Alzheimer’s); interference with apoptosis may contribute to some cancers

Fig.9 show cell apoptosis

The Immune Response

16
Fig.10 show immune response

Conclusion
Cells typically receive signals in chemical form via various signaling molecules.
When a signaling molecule joins with an appropriate receptor on a cell surface, this
binding triggers a chain of events that not only carries the signal to the cell interior,
but amplifies it as well. Cells can also send signaling molecules to other cells. Some
of these chemical signals — including neurotransmitters — travel only a short
distance, but others must go much farther to reach their targets.

17
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21. Cooper, GM (2000). [Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland
(MA): Sinauer Associates; 2000. Functions of Cell Surface Receptors. Available
from: https://www.ncbi.nlm.nih.gov/books/NBK9866/ "The Cell: A Molecular
Approach"] www.ncbi.nlm.nih.gov/books/NBK9866/.

External links
Cell signalling - slideshare
MCB-hormonal signals - slideshare
Content
What Kind of Signals Do Cells Receive 1
How Do Cells Recognize Signals? 2
how Do Cells Respond to Signals? 5
how Do Signals Affect Cell Function? 5
The Role of calcium ions in blood clotting 7
Relationship of hormones and cell signal 10
transduction
Signal Amplification 20
Muscle Contraction uses Calcium as 2nd 20
messenger
Termination of the Signal 21
conclusion 23