Lecture 8 Outline (Ch. 11)
I.
Signal Transduction Pathways
II.
Signaling ranges
III. Three receptor classes (families)
IV. Intracellular receptors
V.
Phosphorylation
cascades
VI. Second messengers
VII. Signal efficiency
VIII. Apoptosis
IX. Summary
Cell Signaling = Signal Transduction
Signal Transduction – receiving a signal & relaying the response
Signal Transduction
Cell phone rings
1
Reception
You listen to
your friend
2
Transduction
You drive
somewhere
3 Response
Receptor
Relay molecules
Activation
of cellular
response
Signaling
molecule
Response variable – examples: mate, organize,
divide, die, grow, send another signal, etc…
Sending the Signal – direct contact
Sending the Signal
Three methods
of cell signaling
over distances:
Signal Transduction
Signal called a ligand
Signaling-molecule binding site
The receptor is a
protein that detects
the signal
Segment that
sends signal inside cell
G-protein coupled receptors (GPCRs)
A 7-pass transmembrane receptor
Links via a G-protein….binds GTP/GDP
Receptor Tyrosine Kinases (RTKs)
Transmembrane receptor – dimerizes when activated
Auto-phosphorylates when active to rely signal
Ligand-gated ion channels
Open when the ligand is bound
Close when signal is not present
Signal Transduction for hydrophobic molecules
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
Hormonereceptor
complex
DNA
DNA
• hydrophobic signals
- Receptor moves to DNA
NUCLEUS
CYTOPLASM
Transduction – relay the signal
• Phosphorylation: adding a phosphate group
• Used to activate proteins already in the cell
Transduction hydrophilic signals – relay the signal
• Dephosphorylation = removing a phosphate group
Signal Transduction for hydrophilic molecules
• hydrophilic signals
Signaling molecule
Receptor alerts
molecules inside the cell
= phosphorylation
Receptor
Activated relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
ADP
Pi
P
Active
protein
kinase
2
PP
Inactive
protein kinase
3
ATP
ADP
Pi
Active
protein
kinase
3
PP
Inactive
protein
P
ATP
P
ADP
Pi
PP
Active
protein
Cellular
response
Signal Transduction for hydrophilic molecules
First messenger
G protein
G protein-coupled
receptor
Adenylyl
cyclase
= small
molecules inside
cell to relay
message
GTP
ATP
• example second
messengers: GTP,
cAMP, ATP, Ca++
• Or use second
messengers
Second
cAMP messenger
Protein
kinase A
Cellular responses
Specificity of cell signaling
Scaffold proteins increase signal efficiency
• Scaffold protein – larger protein for binding and
bringing together several other signal proteins
Response – cell does something
1 mm
Interdigital tissue
Response – ex. No death signal, cell lives
protein (active)
Inhibits activity
Mitochondrion
Receptor
for deathsignaling
molecule
Inactive proteins
(a) No death signal
Apoptosis –
programmed
cell death
- membrane
inverts
- biomolecules
degraded
- organelles
break down
Response – ex. Death signal, cell undergoes apoptosis
Cell
forms
blebs
(inactive)
Deathsignaling
molecule
Active Active
Other
proteases
Caspases
Nucleases
(b) Death signal
Activation
cascade
Signal transduction = reception, transduction, response
Growth factor
Reception
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA