CELL COMMUNICATION

Extracellular

ligand
receptor

Second Transduction cascade

messenger

Response molecules
 TRANSMEMBRANE RECEPTORS

Three types of transmembrane receptor:

1) G-protein-linked receptors
Epinephrine receptor (β-adrenergic receptor)
2) Tyrosine-kinase receptors
Insulin receptor
3) Ligand-gated ion channels
Calcium channels
 G-protein-linked receptors Figure 11.7

A) Called G-protein receptors

because they are linked to relay
proteins that bind guanosine di-
and triphosphate (GDP and
GTP)

B) When the ligand binds, the G-

protein can now bind to the receptor.
Its GDP is replaced by GTP.
This allows the G-protein move along
the membrane to an adjacent
enzyme to activate or inhibit it.

C) The GTP on the G-protein is

then hydrolyzed back to GDP.
This deactivates the G-protein
and it can now begin a new
cycle.
 G-protein-linked receptors Figure 11.6

Where does cAMP fit

into this scheme?
 Figure 11.13
G-protein-linked receptors

Where does cAMP fit

into this scheme?
 Figure 11.13
G-protein-linked receptors

Where does cAMP fit

into this scheme?
 CELL COMMUNICATION

Extracellular

Relay protein

Regulation 1 Transduction cascade

Regulation 2

Response molecules
Figure 11.11 A phosphorylation cascade

cAMP

Regulation 1

Regulation 2
Figure 11.16 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine
Tyrosine Kinase Receptors
These transmembrane receptors are diverse and common.
To function they have two components:
a) a kinase (which is actually part of the receptor itself)
b) a target (or ‘relay’) protein, which is separate from the receptor
A functional receptor has two parts, which dimerize when the ligand
binds. Dimerization activates the kinase part of receptor.
The kinase moves a phosphate group from ATP to a specific amino acid
(tyrosine, serine, or threonine) located within the cytoplasmic part of the
receptor’s polypeptide chain
The protein kinase receptor therefore phosphorylates itself
(autophosphorylation).
When phosphorylated in this manner protein kinase receptors then
activate relay proteins, again by phosphorylation.
Figure 11.8 The structure and function of a tyrosine-kinase receptor
Tyrosine Kinase Receptors
The Insulin Receptor
The insulin receptor consists of two dimers. Each has an α subunit, which
binds the ligand (insulin) outside the cell, and a β subunit, which forms the
transmembrane part of the receptor.
Two molecules of insulin (one for each α subunit) bind to the receptor.
When insulin binds to the α subunit, the receptor dimerizes.
This activates the protein kinase in the β subunit of the receptor, and it auto-
phosphorylates.
Insulin receptors then target and phosphorylate other cytoplasmic proteins
called insulin response substrates.
These proteins then control other cellular activities, including the insertion of
glucose transporters into the cell membrane.
Insulin Receptors
Insulin Receptors
 Figure 11.17

Activation of gene expression

by kinase signaling cascades
Calcium as a Second Messenger

Calcium can activate a large number of different signaling and cellular

proteins.

Its concentration inside the cell is carefully controlled and can be

10,000 times less than what it is outside.

Abrupt increases can trigger a whole series of cellular events.

Calcium acts by binding to calmodulin an abundant intracellular

protein, which is a kinase that can trigger a calcium-dependent
protein kinase cascade.
Calcium as a Second Messenger

Increases in intracellular calcium can occur in two ways:

1) facilitated diffusion through ion channels.
2) the release of calcium from intracellular stores. This can be
controlled by yet another signal transduction cascade that uses
inositol trisphosphate (IP3).
This cascade can be activated either by G-protein-linked receptors
that are not linked to cAMP, or by protein-kinase receptors like the
insulin receptor.
Figure 11.9 A ligand-gated ion-channel receptor
Figure 11.15 Calcium and inositol triphosphate in signaling pathways (Layer 3)
Calcium as a Second Messenger

To terminate Ca2+ signaling, it is removed from the cytoplasm by Ca2+

pumps.
These use ATP to move Ca2+ against the concentration gradient (active
transport).
Ca2+ can be pumped to three places:
1) Out of the cell
2) Into mitochondria
3) Into smooth endoplasmic reticulum
Figure 11.14 The maintenance of calcium ion concentrations in an animal cell

3
The specificity and diversity of cell signaling

Figure 11.18
 CELL COMMUNICATION - REVIEW

Extracellular
The presence of specific receptors determine whether a cell responds to
a signal or not.

There are mechanisms to increase and decrease the activity of a

signaling pathway. For any one pathway, these are specific and separate.

Signals (ligands) can be hydrophilic, in which case their receptors are in

the cell membrane; or hydrophobic, where Relay
receptors are in the cytoplasm.
protein

Transmembrane receptors control signal transduction cascades by way of

Transduction
second messengers, the most important of which are cAMP,cascade
Ca2+, and IP3

Signal transduction cascades that are activated by second messengers

are made up of many different types of kinase enzymes.
Response molecules
There are three major types of transmembrane receptor: G-protein
receptors, protein-kinase receptors, and ligand gated ion channels.
 CELL COMMUNICATION - REVIEW

The presence of specific receptors determine whether a cell responds to

a signal or not.

There are mechanisms to increase and decrease the activity of a

signaling pathway. For any one pathway, these are specific and separate.

Signals (ligands) can be hydrophilic, in which case their receptors are in

the cell membrane; or hydrophobic, where receptors are in the cytoplasm.

Transmembrane receptors control signal transduction cascades by way of

second messengers, the most important of which are cAMP, Ca2+, and IP3

Signal transduction cascades that are activated by second messengers

are made up of many different types of kinase enzymes.

There are three major types of transmembrane receptor: G-protein

receptors, tyrosine-kinase receptors, and ligand gated ion channels.
 CELL COMMUNICATION - REVIEW

G-protein receptors use G-proteins as relay molecules to control adenylyl

cyclase, and therefore the concentration of cAMP.

Tyrosine kinase receptors are dimers that autophosphorylate and then

activate other relay molecules.

Intracellular calcium concentrations are controlled by ligand-gated ion

channels, and calcium pumps.

IP3 can open calcium channels on the endoplasmic reticulum to release

calcium into the cytoplasm.

Calcium controls enzyme activation states and gene expression by way of

signal transduction cascades initiated when it binds to calmodulin.

Steroid receptors are cytoplasmic and translocate to the nucleus when

the ligand binds. They control the gene expression. They can also interact
with protein kinase cascades (crosstalk).
Figure 11.10

Steroid hormones use intracellular

(cytoplasmic) receptors to control:
1) Gene expression
2) Other intracellular signalling pathways
(crosstalk)
 1

1) Diffusion of steroids into the cell

2) Binds to a receptor leading to a
change in its conformation. 2
3) Moves into nucleus aided by a
chaperone protein
4) Controls expression of genes 3