Transcript 11 Signal Transduction

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3.D.3 Signal Transduction
Signal transduction pathways link
signal reception with cellular
response.
Many chemical messengers cannot
cross the plasma membrane.
Signal transduction is the process by
which an extracellular signal is
converted to an intracellular response.
Signaling begins with the recognition of a
chemical messenger, a ligand, by a
receptor protein.
A ligand can be:
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Ions
Proteins (hormones)
Neurotransmitters
Steroids
Many other types
Different receptors recognize different
ligands in a specific one-to-one
relationship.
When a ligand binds to a receptor, it
causes the receptor protein’s shape to
change (conformational change).
The conformational change of the
receptor initiates transduction of the
signal.
Types of
Receptors:
G Protein
Receptors
Ligand-gated
Ion Channels
Receptor
Tyrosine Kinases
G-protein coupled
receptors
- Receptor in PM with
7 alpha helices
- Works with another
protein that binds the
energy-rich GTP
• G-protein on cytoplasmic side (loosely bound) acts like
on/off switch
– GDP bound= off
– GTP bound=on
• G-protein usually works with receptor and an enzyme
• Ligand binds to extracellular side of receptor
• Causes a conformational change on cytoplasmic
side, which binds the inactive G-protein
• Binding causes GTP to replace GDP
• The G-protein activates
• The active G-protein dissociates and diffuses along
the membrane
• Binds the enzyme, which alters its shape and
activity
• The active enzyme triggers the next step
• The G-protein also acts as its own GTPase enzyme
– Hydrolyzes its GTP to GDP
– Inactivates the G-protein
• Returns to original state for re-use
G Protein-Coupled Receptors
• Used in:
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Yeast mating factors
Epinephrine and many other hormones
Neurotransmitters
Embryonic development
Sensory reception (vision, smell in humans)
• Involved in many human diseases
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Cholera
Whooping cough
Botulism
Others
Types of
Receptors:
G Protein
Receptors
Ligand-gated
Ion Channels
Receptor
Tyrosine Kinases
Ligand-Gated Ion Channels
(Ion Channel Receptors)
- Membrane receptor has a
“gate”
- Ligand binds specific site
on extracellular side
Ligand-Gated Ion Channels
(Ion Channel Receptors)
- The gate opens or closes
- Rapid changes in ion
concentration causes a
response
Ligand-Gated Ion Channels
(Ion Channel Receptors)
- Very important in nervous
system
- Some are controlled by
electrical signals instead of
ligands (voltage-gated ion
channels)
Ligand-gated Ion Channels:
Model: the Sodium Channel
The ligand that binds to the ion-gated
sodium channel is the neurotransmitter
acetylcholine.
The sodium channel is closed when
acetylcholine is not bound to the receptor.
The sodium channel opens when
acetylcholine is bound the receptor site.
Sodium is then able to diffuse into the
cell down its concentration gradient.
Types of
Receptors:
G Protein
Receptors
Ligand-gated
Ion Channels
Receptor
Tyrosine Kinases
Receptor Tyrosine
Kinases
- Kinase= enzyme that
catalyzes the transfer of
phosphate groups
- Tyrosine kinase receptors=
attach phosphates to
tyrosines (a kind of amino
acid) on a substrate protein
• Prior to the ligand binding, the receptors are
individual polypeptides
– Alpha-helix part spans membrane
– Tails inside cell with many tyrosines
• Signal binds (such as a growth factor)
• The two receptor polypeptides associate closely and
form a dimer (dimerization)
• Dimerization activates the tyrosine kinase region of
each polypeptide
• Each TK adds a phosphate from an ATP to a tyrosine
on the tail of the other polypeptide
• The receptor is fully activated as a result
• Specific relay proteins recognize it
• Each protein binds to a specific phosphorylated
tyrosine
• Binding changes the shape of each protein and
activates it
• Each activated protein triggers a transduction
pathway
• **One RTK complex can activate 10+ transduction
pathways and cellular responses!
• Cell growth and cell reproduction are often
controlled by Receptor Tyrosine Kinases
• Abnormal RTKs that function without ligands may
contribute to some cancers
INTRACELLULAR RECEPTORS
Intracellular Receptors
• Found in the cytoplasm or nucleus
• Must be reached by molecules that are:
– Small enough, or
– Hydrophobic enough
Intracellular Receptors
• Molecules that can do this:
– Steroid hormones (testosterone, estrogen, etc)
– Thyroid hormones
– Nitric oxide (NO)
Hormone example
• Hormone binds with
receptor
• Complex reaches the
nucleus
• Binds to specific genes
• The bound protein acts as
a transcription factor“calls in” the machinery to
copy the gene and
translate it into a protein
SUMMARY
Ligands interact with receptors to
initiate a sequence inside the cell.
An Example Signal Transduction Pathway
Signaling cascades often amplify the
incoming signals, with the result of
appropriate responses by the cell.
Second messengers are often essential
to the function of the cascade.
Many signal transduction pathways cause:
• Protein modifications such as methylation
that change the signaling process and regulate
cell processes.
• Phosphorylation cascades that amplify the
signal.