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
Lecture 8 Outline (Ch. 11)
Cell Signaling = Signal Transduction
Signal Transduction – receiving a signal & relaying the response
Reception Transduction Response
Receptor
Relay molecules
Signalingmolecule
Activationof cellularresponse
1 2 3
Signal Transduction
Cell phone rings You listen to your friend
You drive somewhere
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
Signaling-molecule binding site
Segment thatsends signal inside cell
The receptor is a protein that detects the signal
Signal called a ligand
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
Receptorprotein
Hormone(testosterone)
EXTRACELLULARFLUID
Plasmamembrane
Hormone-receptorcomplex
DNA
Hormone(testosterone)
EXTRACELLULARFLUID
Receptorprotein
Plasmamembrane
Hormone-receptorcomplex
DNA
NUCLEUS
CYTOPLASM
• hydrophobic signals
- Receptor moves to DNA
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
Signaling molecule
ReceptorActivated relaymolecule
Inactiveprotein kinase
1 Activeproteinkinase
1
Inactiveprotein kinase
2
ATPADP Active
proteinkinase
2
P
PPP
Inactiveprotein kinase
3
ATPADP Active
proteinkinase
3
P
PPP
i
ATPADP P
ActiveproteinPP
P i
Inactiveprotein
Cellularresponse
Phosphorylation cascadei
• hydrophilic signals
Receptor alerts molecules inside the cell = phosphorylation
Signal Transduction for hydrophilic molecules
First messenger
G proteinAdenylylcyclase
GTP
ATPcAMP
Secondmessenger
Proteinkinase A
G protein-coupledreceptor
Cellular responses
• Or use second messengers
= small molecules inside cell to relay message
• example second messengers: GTP, cAMP, ATP, Ca++
Signal Transduction for hydrophilic molecules
Specificity of cell signaling
Scaffold proteins increase signal efficiency
• Scaffold protein – larger protein for binding and bringing together several other signal proteins
Interdigital tissue
1 mm
Response – cell does something
protein (active)Inhibits activity
Mitochondrion
Receptorfor death-signalingmolecule
Inactive proteins
(a) No death signal
Response – ex. No death signal, cell lives
Apoptosis – programmed cell death
- membrane inverts- biomolecules degraded- organelles break down
(b) Death signal
Death-signalingmolecule
(inactive)Cellformsblebs
Active Active
Activationcascade
Otherproteases
Nucleases
Response – ex. Death signal, cell undergoes apoptosis
Caspases
Growth factor
Receptor
Phosphorylationcascade
Reception
Transduction
Activetranscriptionfactor
ResponseP
Inactivetranscriptionfactor
CYTOPLASM
DNA
NUCLEUS mRNA
Gene
Signal transduction = reception, transduction, response
