Signal Transmission & Gene
Expression
AKA – Cell Signaling Basics
(we will revisit this topic during body systems)
Signal Transduction Pathway
•
“Signal” = chemical message
that moves throughout body
•
2 types of signal
transmissions
–
Intercellular – move from
cell to cell to cell
•
–
Ex: Hormones of endocrine
system, neurotransmitters of
nervous system
Intracellular – move within
cell itself
•
Ex: Apoptotic pathway
(mitochondrial mediated)
•
Chemical messages (“signals”) can affect cell in
two ways:
1. Immediate effect on cell function (change what cell
is doing)
2. Lead to gene expression via DNA transcription and
protein translation
1. Immediate Affect
•
A message (chemical signal) is transduced (and
usually amplified) into actions within cell
•
Usually initiates a phosphorylation cascade
which passes an energy-rich phosphate from
one protein to another to another until desired
action is carried out
Generic Pathway
•
Reception – Chemical message (ligand)
docks at receptor on cell membrane and
changes its shape
•
Transduction – switching message from
chemical signal received on cell outside to
chemical messages on interior of cell
•
Response – Signal transduction cascade
occurs until end result is reached
Ex: Epinephrine Signaling
•
Epinephrine (ligand) is released by adrenal
gland during “fight or flight” response
–
Ligand is a chemical that can't get through cell
membrane thus binds receptor on outside
•
Epinephrine travels through body and binds to
receptors on the outside of liver cells (high
storage of glycogen)
•
Epinephrine receptor is a G-protein coupled
receptor
•
G-protein is embedded within cell membrane;
has three subunits inside the cell
•
Ligand binding changes the conformation of the
GPCR and causes it to release alpha subunit
•
Alpha subunit moves to another protein called
adenylyl cyclase
•
Binding causes conformational change
which activates protein (enzyme)
•
Enzyme converts ATP → cAMP
•
cAMP – (secondary messenger) targets a protein
kinase that has 4 subunits
•
2 catalytic (speed up rxn rate)
•
2 regulatory (regulate catalytic subunits)
–
If reg. subunits are attached to cat. → no action
–
cAMP binds to regulatory subunits  allosteric
change in protein  catalytic subunits are released
•
Catalytic subunits get phosphorylated (activated)
•
Active catalytic subunits act on enzymes w/in cell
•
In this example, they activate phosphorylase,
which breaks apart glycogen to release
glucose
Why bother with all these steps?
2. Change Gene Expression
•
Pathway is the same UNTIL the catalytic
subunits are activated
•
There are no proteins for these to act on, so
instead they activate CREB (a transcription
factor)
•
CREB binds to DNA upstream of gene to be
expressed, bends DNA to facilitate transcription
of mRNA, mRNA is translated into a protein
called phosphatase which is able to break down
glycogen
Changes to Pathways
• “Correct” signal transduction pathways are
under strong selective pressure
• Changes that result in ineffective pathways are
generally bad.
• 2 examples:
• Diabetes
• Botulism toxin
Ex: Diabetes Type I
• Mutation results in autoimmune destruction of
pancreatic beta cells (insulin producing cells)
• Inability to produce insulin affects ability of
glucose to enter cells
Ex: Botulinum Toxin (BTX)
• Caused by bacterium
Clostridium botulinum
• Toxin inhibits
acetylcholine nt (signal)
from being released
thus inhibiting muscle
contraction
• Leads to paralysis