Chapter 1
Aspects of Cellular Signalling
(Signaling)
Chapter Objectives
• Understand the general principles governing
cellular signaling
– Good signals
– Types of signaling
– Amplification of signals
– Control of signals
– Adaptor molecules
Importance
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Cells must be able to sense environment
Cells must react to environment
Single celled organisms pass signals
Multicellular organisms have similar signals
Normal state compared to disease state
Rapid growth of the field
– March, 2009 – 361,604 hits
– Oct, 2013 – 527,279 hits
Main Principles
• Signal arrives at cell
surface
• Signal is passed to inside
of cell
• Signal is propagated
inside the cell “cascade”
• Message reaches final
destination
• Cell does a response to
signal
Nucleus
receptor
New proteins
Cytoplasm
organelle
Difficulty with Pathways
• Pathways are not linear
– One signal can activate many pathways
• Cells receive more than one signal at a time
– How do they integrate?
• Amplification of signals is often necessary
Good Signals
• Must have specificity
• Small and have rapid
diffusion (usually)
• Rapidly created
– From a common source
(ATP?)
– Sequestered for later
use
• Can be turned off
quickly
Enzyme
Cell
Enzyme
Cell
Types of Cell Signaling
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Electrical – synaptic
Endocrine
Paracrine
Autocrine
Cell-Cell
– Receptor-ligand
– Gap Junctions
Electrical Signals
Synapses – receive signals from other cells
Axon terminal – sends signals to next cell
Endo/para/auto-crine signaling
• Endocrine – signal from one cell effect a cell
far away
• Paracrine – signal from one cell effect a cell
nearby
• Autocrine – signal from one cell effect itself
Signaling cell
Target cell
Target cell
Non-Target cell
Receptor Ligand Signaling
• One cell has receptor – one cell has ligand
In flies …
ligand
receptor
RTK
Bride of sevenless
Boss
Sevenless
Sev
Second messenger
Son of sevenless
Sos
Gap Junctions
Many isoforms of connexin
Gaps size is dictated by connexin isoform
Allows approximately <1200 Da chemicals through
Signal Amplification
Second messenger
Second messenger
Second messenger
Kinase
Kinase
Kinase
Phosphorylation
Phosphorylation
Phosphorylation
Phosphorylation
Phosphorylation
Phosphorylation
Phosphorylation
Phosphorylation
Phosphorylation
Active enzymes Active enzymes
Active enzymes Active enzymes Active enzymes
Active enzymes
Lots of Product!!
Active enzymes Active enzymes
Active enzymes
Coordination of Signals
Receptor 1
Receptor 2
Receptor
A
B
G
B
C
D
H
C
E
Effect
K
A
Effect
F
Effect
Effect
Scaffolding Proteins?
• Why is there no long range signal
amplification in cells? Diffusion?
Domains
• Catalytic
• Regulatory
• Specific Function
– EF-hand
• Ca2+ binding
– SH2 and SH3
• Protein/protein
– PH (Pleckstrin homology)
• Protein/protein
– 14-3-3
• Protein/protein
• Regulation
Oncogenes
• Genes that lead to cancer
• Many are cell signaling molecules
• Four Classes
– Class 1
• Platlet growth factors
– Class 2
• Epidermal and nerve growth factors
– Class 3
• Cytosolic kinases
– Class 4
• Nuclear transcription factors