Cell-Cell Interactions

Cell Communication
Communication between cells requires:
ligand: the signaling molecule
receptor protein: the molecule to which the
receptor binds
- may be on the plasma membrane or within
the cell

Cell Signaling

Cell Signals
Direct contact
Paracrine signaling
Endocrine signaling
hormones
Synaptic signaling
neurotransmitters

Cell Communication
Direct contact
molecules on the
surface of one cell are
recognized by
receptors on the
adjacent cell

Cell Communication
Paracrine signaling
signal released
from a cell has an
effect on
neighboring cells

Cell Communication
Endocrine signaling
hormones
released from a
cell affect other
cells throughout
the body

Cell Communication
Synaptic signaling nerve
cells release the signal
(neurotransmitter) which
binds to receptors on
nearby cells

Signal transduction
Events within the cell that occur in response

to a signal
When a ligand binds to a receptor protein, the
cell has a response
Different cell types can respond differently to
the same signal
Epinephrine example

Cell Communication
A cells response to a signal often involves
activating or inactivating proteins.
Phosphorylation is a common way to
change the activity of a protein.
protein kinase an enzyme that adds a
phosphate to a protein
phosphatase an enzyme that removes a
phosphate from a protein

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Protein
Phosphorylation

Two classes: serine/threonine kinases or tyrosine

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Receptor Protein
Receptor proteins have a three-dimensional

shape that fits a specific signal molecule.

When a signal molecule and receptor protein

bind, a change in the receptor protein is

induced and a response in the cell is
generated.
There is a conformational change that arises
from the ligand binding to the receptor
Receptor-ligand complex can directly or
indirectly interact with a whole host of other
signaling molecules within the cell

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Receptor Types
Receptors can be defined by their location.
intracellular receptor located within the

cell
cell surface receptor or membrane receptor

located on the plasma membrane to bind a

ligand outside the cell

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Cell Surface Receptors

There are 3 subclasses of membrane
receptors:
1. channel linked receptors ion channel
that opens in response to a ligand
2. enzymatic receptors receptor is an
enzyme that is activated by the ligand
3. G protein-coupled receptor a G-protein
(bound to GTP) assists in transmitting
the signal

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Cell Surface Receptors

Chemically gated ion channels

Enzymatic receptors

GPCR
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G proteins
Ras and Trimeric G protein
Ras is monomeric
Trimeric has 3 subunits alpha, beta and

gamma
Both of them bind GTP in their active form
and bind GDP in their inactive form

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G-Protein Coupled Receptors

G-protein protein bound to GTP or GDP
G protein exists in two forms active ( GTP bound)
and inactive (GDP bound)
G protein is trimeric (3 subunits alpha, beta , and
gamma)
The guanine nucleotide is bound to the alpha
subunit
G-protein-coupled receptor (GPCRs) receptors
bound to G proteins
- G-protein is a switch turned on by the receptor
- G-protein then activates an effector protein
(usually an enzyme)
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G-Protein Coupled Receptors

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G-Protein Coupled Receptors

Once activated, the effector protein produces a second
messenger.
- second messenger generates the cellular response to
the original signal
For example one common effector protein is adenylyl
cyclase which produces cAMP as a second messenger.
cAMP binds to Protein Kinase A and activates it

Another common effector protein is PhospholipaseC

PIP2 is acted on by effector protein phospholipase C
Produces IP3 ( Inositol Tris phosphate) plus DAG(Diacyl

glycerol)
Both act as second messengers

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cAMP Signaling
Pathway

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Calcium
Ca2+ serves widely as

second messenger
Intracellular levels
normally low
Extracellular levels
quite high
Endoplasmic reticulum
has receptor proteins
that act as ion
channels to release
Ca2+
Most common receptor
binds IP3
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Amplifying the Signal

Most signaling molecules exist in such

low concentration, diffusion across the

cytoplasm requires amplification.
A single cell surface receptor can

stimulate a cascade of protein kinases to

amplify the signal.

causes a strong response inside the cell to a

weak signal outside

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Different receptors can produce the same

second messengers
Hormones glucagon and epinephrine can both
stimulate liver cells to mobilize glucose
Different signals, same effect
Both act by same signal transduction pathway

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Single signaling molecule can have different

effects in different cells

Existence of multiple forms of the same
receptor (subtypes or isoforms)
Receptor for epinephrine has 9 isoforms
Encoded by different genes
Sequences are similar but differ in their

cytoplasmic domains

Different isoforms activate different G proteins

leading to different signal transduction

pathways

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Intracellular Receptors
A steroid hormone receptor has three
functional domains:
1. hormone-binding domain
2. DNA binding domain
3. domain that interacts with co-activators
to affect gene expression

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Intracellular Receptors
Intracellular receptors are located within

the cell, and trigger a variety of responses,

depending on the receptor.
acting as gene regulators
acting as enzymes

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Regulation of Gene Transcription by

Intracellular Receptors
Cortisol
Inhibitor
Transcription
activating
domain
DNA binding site blocked

Signal moleculebinding domain

DNA binding site exposed

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Intracellular Receptors

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Coactivators
Target cells response to a lipid-soluble cell

signal can vary enormously, depending on the

nature of the cell
Even the same type of cell may have different
responses
Depends on coactivators present
Estrogen has different effects in uterine tissue
than mammary tissue
Not presence or absence of receptor
Presence or absence of coactivator
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Receptor Kinases (receptors

with enzymatic function)
receptor tyrosine kinases
- membrane receptor
- when bound by a ligand, the receptor is
activated by dimerization and
autophosphorylation
- activated receptor adds a phosphate to
tyrosine on a response protein
- an example is the insulin receptor

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Activation of Receptor Tyrosine

Kinase

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Insulin receptor
Activated receptor

has phosphorylated
sites that allow
docking
Insulin is a hormone
that helps to
maintain a constant
blood glucose level
Lowers blood
glucose
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Kinase cascade
Mitogen-activated protein (MAP) kinases
Important class of cytoplasmic kinases
Mitogens stimulate cell division
Activated by a signaling module called a
phosphorylation cascade or kinase cascade
Series of protein kinases that phosphorylate
each other in succession
Amplifies the signal because a few signal
molecules can elicit a large cell response

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Ras proteins
Small GTP-binding protein (G protein)
Link between the RTK and the MAP kinase

cascade
Ras protein is mutated in many human
tumors, indicative of its central role in linking
growth factor receptors to their cellular
response
Ras can regulate itself stimulation by growth
factors is short-lived
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Scaffold proteins
Thought to organize the

components of a kinase
cascade into a single
protein complex
Binds to each individual
kinase such that they
are spatially organized
for optimal function
Benefit in efficiancy
Disadvantage in
reducing amplification
effect
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Expression of Cell Identity

Cells contain an array of marker proteins

located on the cell surface.

glycolipids - tissue-specific cell surface
markers
Major histocompatibility complex (MHC)
proteins - identify self versus non-self cells

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