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CHAPTER 9
LECTURE
SLIDES
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Cell Communication
Chapter 9
Overview
• Communication between cells requires
• Ligand – signaling molecule
• Receptor protein – molecule to which the
receptor binds
• Interaction of these two components
initiates the process of signal transduction,
which converts the information in the
signal into a cellular response
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4
• There are four basic mechanisms for
cellular communication
1.Direct contact
2.Paracrine signaling
3.Endocrine signaling
4.Synaptic signaling
• Some cells send signals to themselves
(autocrine signaling)
5
• Direct contact
• Molecules on the
surface of one cell are
recognized by
receptors on the
adjacent cell
• Important in early
development
• Gap junctions
6
• Paracrine signaling
• Signal released from
a cell has an effect on
neighboring cells
• Important in early
development
• Coordinates clusters
of neighboring cells
• Signaling between
immune cells
7
• Endocrine signaling
• Hormones released
from a cell travel
through circulatory
system to affect other
cells throughout the
body
• Both animals and
plants use this
mechanism extensively
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• Synaptic signaling
• Animals
• Nerve cells release
the signal
(neurotransmitter)
which binds to
receptors on nearby
cells
• Association of neuron
and target cell is a
chemical synapse
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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
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Phosphorylation
• Addition of phosphate group
• A cell’s 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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Receptor Types
• Receptors can be defined by their location
1.Intracellular receptor – located within the
cell
2.Cell surface receptor or membrane
receptor – located on the plasma
membrane to bind a ligand outside the cell
– Transmembrane protein in contact with both
the cytoplasm and the extracellular
environment
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3 subclasses of membrane
receptors
1. Chemically gated ion channels – channellinked receptors that open to let a specific
ion pass in response to a ligand
2. Enzymatic receptors – receptor is an
enzyme that is activated by the ligand
– Almost all are protein kinases
3. G protein-coupled receptor – a G-protein
(bound to GTP) assists in transmitting the
signal from receptor to enzyme (effector)
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Intracellular Receptors
• Steroid hormones
– Common nonpolar, lipid-soluble structure
– Can cross the plasma membrane to a steroid
receptor
– Binding of the hormone to the receptor
causes the complex to shift from the
cytoplasm to the nucleus
– Act as regulators of gene expression
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• A steroid receptor has 3 functional
domains
1.Hormone-binding domain
2.DNA-binding domain
3.Domain that interacts with coactivators to
affect level of gene transcription
• In its inactive state, the receptor typically
cannot bind to DNA because an inhibitor
protein occupies the DNA binding site
• Binding of ligand changes conformation
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Coactivators
• Target cell’s 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
• Protein kinases phosphorylate proteins to
alter protein function
• Receptor tyrosine kinases (RTK)
– Influence cell cycle, cell migration, cell
metabolism, and cell proliferation
• Alteration to function can lead to cancer
– Membrane receptor
– Plants possess receptors with a similar overall
structure and function
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• RTKs have
– A single transmembrane domain
• Anchors them in membrane
– Extracellular ligand-binding domain
– Intracellular kinase domain
• Catalytic site of receptor acts as protein kinase
• When a ligand binds, dimerization and
autophosphorylation occur
• Cellular response follows – depends on
cellular response proteins
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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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G-Protein Coupled Receptors
G-protein – protein bound to GTP
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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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
29
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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G-Protein Coupled Receptors
• Single largest category of receptor type in
animal cells is GPCRs
• Receptors act by coupling with a G protein
• G protein provides link between receptor
that receives signal and effector protein
that produces cellular response
• All G proteins are active when bound to
GTP and inactive when bound to GDP
• Effector proteins are usually enzymes
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• Often, the effector proteins activated by G
proteins produce a second messenger
• 2 common effectors
1. Adenylyl cyclase
– Produces cAMP
– cAMP binds to and activates the enzyme protein
kinase A (PKA)
– PKA adds phosphates to specific proteins
2. Phospholipase C
– PIP2 is acted on by effector protein phospholipase C
– Produces IP3 plus DAG
– Both act as second messengers
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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
37
Cell-to-Cell Interactions
Cells can identify each other by cell surface
markers
-Glycolipids are commonly used as tissuespecific markers
-Major histocompatibility complex (MHC)
proteins are used by cells to distinguish
“self” from “nonself”
38
• 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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