Cell Communication Presented By :

Dr.Tareq Abu-Libdeh
➢ Cell signaling:
₋ Living cells in a multicellular organism have to communicate e each other in order
to maintain homeostasis & life.
₋ Cells communicate e each through signals which result in responses within the cells
₋ The cell signaling system has 3 parts:
1. Reception
2. Transduction
3. Response

The signal transduction pathway: is a

series of steps by which a signal received
on a cell’s surface is converted into a
specific cellular metabolic activity which
result in specific cell response

(1)

(2)

(3)
Steps of signaling system
 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh

₋ The signals can be received from either:

1. External environment:
✓ Sound
✓ Light
✓ Temperature
✓ Odorants
✓ Substances that we taste All these factors will cause the cell
2. Within the body (hormones): to respond in some way.
✓ Epinephrine (Adrenaline)
✓ Insulin
✓ Testosterone
✓ Estrogen

₋ Modes of cell signaling

1. Intracrine: hormones or growth factors act on receptors inside the
cell (cytosolic /nuclear receptors)

2. Autocrine : the cell secretes a hormone or

chemical substance that binds to receptors
on that surface of same cell, leading to
changes in the cell.
(Autocrine signaling plays critical roles in
cancer activation)

3. Direct (Juxtacrine signaling): gap junctions

(Cardiac muscles, embryonic development)
Juxtracrine or contact /dependent signaling
:is a type of cell-cell
or cell matrix signaling in multicellular organism
 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh
• Types of juxtracrine signaling:
a) A membrane ligand & a membrane protein of two adjacent
cells interact
b) Communicating junction(gap J) links the intracellular
compartments of two adjacent cells allowing the
exchange of small molecules

c) An extracellular matrix protein & a cell membrane protein

interact
 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh
4. Short distance: act locally on different nearby cells:
ₒ Paracrine (nearby) signaling (cytokines, histamine)
ₒ Synaptic signaling (neurotransmitters : AC)

▪ Paracrine: signals are carried by messenger molecules called "local regulators", that are
released by one cell and move to make contact with another nearby cells
(e.g.; blood clotting, local allergic skin reaction, wound healing)

▪ Synaptic: (neurotransmitters). Neurotransmitters are endogenous chemicals that

transmit signals from a neuron to another nerve cells or muscle cells across the synapse.

LOCAL OR SHORT DISTANT SIGNALING

 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh

Allergic reaction

Wound healing Synaptic signaling

 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh
5. Endocrine signaling: act on target cells at distant body sites
(long distance) e.g. (Hormones produced by endocrine cells,
travel through the circulatory system to affect other cells all
over the body

➢ Reception (remember: it’s the first part of cell signaling)

₋ Signaling molecules: are either secreted by or expressed on the surface of some cells will bind to
receptors on other cells causing changes in target cells

₋ Receptors: Protein molecules found either:

✓ On the cell surface (embedded within the cell membrane)
✓ Inside the cell in ( cytoplasm or nucleus )

Signaling molecules :
are either secreted by or expressed on
the surface of some cells ( plasma
membrane binding molecule)
 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh

₋ Signaling molecules (Ligands): could be: proteins, small peptides, amino acids, nucleotides,
steroids, retinoid (Vit. A), fatty acid derivatives, nitric oxide, carbon monoxide….
( Hormones, neurotransmitters, drugs, toxins, gases)

₋ Ligand: signal molecule with a “key” that fit with the receptor “Lock”
→ Ligand – Receptor complex→ biological changes in the cell

Receptors are integral proteins

embedded in the lipid bilayer of the
cell membrane
 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh
➢ Types /Mechanism of action of hormones
a) Amino acid derivatives: Melatonin
b) Peptide/ protein (non-steroid) hormones:
E.g. : Insulin, glucagon, epinephrine, LH, FSH,
Histamine, Ach, ..… etc.
c) Steroid hormones: E.g. Estrogen, Testosterone,
Aldosterone, Calcitriol, Vit D, cortisol…. etc.

▪ the message carried by the signaling molecule will relayed either

as either alteration in protein function
or alteration in protein synthesis of the cell

Hydrophilic ligand Lipophilic ligand

Peptide based hormones are water soluble Steroid based hormones are lipid soluble
 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh
Intracellular receptors
• They are Proteins found in the
cytoplasm or nucleus of target cells

• The small, hydrophobic Ligands can

easily cross the lipid bilayer
membrane and activate these
receptors ,e.g. steroid and thyroid
hormones

• The ligand –receptor complex moves

to the nucleus → binds to specific
regulatory regions of the
chromosomal DNA → promote the
initiation of transcription of m-RNA (mediate gene expression

Gene expression
Transforming the information on cell’s
DNA into a sequence of amino acids
that ultimately forms a protein

Extracellular receptors:
There are 3 types of membrane receptors
1. G protein–coupled receptors (7–transmembrane protein)
2. Tyrosine kinases (enzyme – linked) receptors
3. Ion channel receptor

1 2 3
 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh

1) G- protein coupled receptors

✓ Step 1: G protein – linked receptors
+ ligand → activate a membrane
protein called G- protein

✓ Step 2: Binding of the ligand to the receptor

changes the shape of the receptor→ release
GTP that
attach to the G protein → ON switch →
activates G protein: G protein is active

✓ Step 3: The activated G protein moves to

catalyze the Adenylyl cyclase enzyme.
The activated
enzyme will change ATP→ cAMP →
is a 2nd messenger→
phosphorylation cascade → cellular response

✓ Step 4: G protein returns to the inactive form by moving away from the enzyme & rejoined with GDP. The
whole system is ready to receive new signal.

• Importance of G protein-coupled receptor system:

3
a) Most widespread class of receptors in mammals

b) Regulates the process of transcription, , motility, secretion,

embryonic development, homeostasis, memory

c) Play significant role in controlling vision, smell & taste,

hearing sensations

d) 45% of all Pharmaceutical & therapeutics targets & interact e

G protein system.

e) Ligand binding produces signaling to a 2ndmessenger

 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh
2) Tyrosine kinase receptors
✓ Step 1:
₋ TK are receptor proteins located in the cell membrane.
₋ Its intracellular domains are associated with an enzyme
₋ start out as inactive monomers.
₋ Each has a ligand binding site
₋ The signal molecules are often growth factors

✓ Step 2:
₋ When signal molecules bind with receptor sites, monomers combine to form dimers → shape in
change of TK → start activation, yet not phosphorylated

✓ Step 3:
₋ Dimerization activates
→ phosphorylation process( it
takes multiple ATPs {6})

₋ Fully phosphorylation
→ fully active receptors

✓ Step 4:
₋ Fully phosphorylated & active receptor → initiate signal transduction → multiple
cellular response
₋ Each TK system can trigger many separate cellular responses

Importance of Tyrosine kinase receptor system

a) One receptor tyrosine kinase (DIMER) can activate more different responses, providing a way for
cells to regulate growth activities
b) Kinase: is the enzyme that catalyze the transfer of phosphate group → phosphorylation of
the Dimer cause ON or OFF

c) Many cancers are caused by mutated tyrosine receptors which get activated without a signal
molecule (cells growing out of control)
 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh
3 ) Ion channel receptors
₋ Are the simplest form of receptors
₋ Also known as ligand-gated ion channels located on post synaptic membrane in nervous system
₋ Is away to regulate facilitated diffusion

Importance of ion channel receptors

a) Important in the nervous system
b) Neurotransmitters function as ligands which
bind to receptors on target cell
c) These receptors are ion channel receptors
d) Once open, ions flow into the target cell
e) Change in ion concentration triggers a
nerve impulse

II. Signal transduction (remember: it’s the second part of cell signaling)
₋ Is the step between receiving of a signal & response of the cell to that signal
₋ is a biochemical chain of events occurring inside the cell
 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh
▪ Role of protein kinase:
✓ They are protein molecules found in the cytoplasm
✓ Act as catalysts
✓ they are inactive until they are phosphorylated
✓ Each activated PK activates the next one in the chain → Phosphorylation cascade
✓ Finally, a protein is activated which generates a cellular response

➢ Second messengers
₋ 1st messenger is the extra- cellular signal molecule (ligand)

₋ 2nd messengers are non-protein molecules that involve in the transduce of signals
inside cells (used to relay messages), used to amplify the signal

₋ Examples of 2nd messengers are:

1. cAMP
2. cGMP
3. Calcium ions
4. Inositol triphosphate (IP3)
 Cell Communication Presented By :
Dr.Tareq Abu-Libdeh

III. Responses: (remember: it’s the Third part of cell signaling)

Cells respond to signaling pathways by many ways:
1. Metabolic enzyme→ alter metabolism
2. Regulatory protein→ alter gene expression
3. Cytoskeletal protein → alter cell shape or movement