1. Ch 11: Cell communication
1st concept: External signals from other cells are converted into responses within a cell
When does it start? ?
Periferal protein and a ligand
watch

2. Signal transduction pathways
Can cause cellular responses using chemical signals that touch the surface of the cell…
The chemistry is similar from microbes and mammals, suggesting an early origin of this biochemistry

3. Evolution of Cell Signaling
Yeast cells
Identify their mates by cell signaling
Receptors
Secrete mating factors. 1
Mating.
New a/ cell. 2 3
 factor
Yeast cell,
mating type a
mating type  
a/ a

4. Animal and plant cells, compared…
Have cell junctions that directly connect the cytoplasm of adjacent cells, allowing communication
Plasmodesmata
Gap junctions
Cell junctions.

5. animal cells may communicate via direct contact, without gap junctions
(b) Cell-cell recognition proteins

6. In other cases, animal cells
Communicate using localized chemical messengers (nearby communication)
Paracrine signaling
Synaptic signaling.
diffusion
Neuro-
transmitter

7. Long-distance signaling
Hormone travels
in bloodstream
to target cells
Blood
vessel
Target
Cells
RESPOND
Endocrine cell
Plants and animals both use hormones for long-distance communication (signaling)

8. Earl Sutherland
suggested that cells receiving [ chemical ] signals went through three processes:
Reception (of a chem. signal)
Transduction (change a signal from 1 form to another)
Response

9. Simplified overview of cell signaling (communication)
Receptor
Relay molecules
CYTOPLASM
cellular
response
Reception
Transduction
Response
Signal
molecule
Pathway!

10. The extracellular signal molecule is a type of
Ligand. Intercellular proteins that bind to receptors triggering cellular responses
Binding causes a conformational change in a receptor (a change in shape)

11. Intracellular transduction signals
Signal molecules that are small or hydrophobic may freely diffuse across the cell membrane and directly initiate cellular metabolic responses

12. Example: Steroid hormones (hydrophobic)
intracellular signalers
Hormone
(testosterone)
Receptor
protein
DNA
mRNA
NUCLEUS
CYTOPLASM
New protein 1
passes through the
plasma membrane.
Activates a receptor 2
Complex enters nucleus
activates a gene
Protein synthesized

13. Receptors in the Plasma Membrane
Three main types
G-protein linked receptors
Tyrosine kinases
Ion receptor channels

14. G-protein-linked receptors
Enzyme
G-protein (switched off)
Cellular response
Activated!
Activated
Signal
interacts with
G proteins
GDP
GTP P
Signal-binding site
If ATP =… what does GTP =?
G-protein (switched on)

15. Receptor tyrosine kinases
Signal protein
Tyrosines
Helix
Tyr
Dimer
Receptor tyrosine kinase proteins P
Shapes match!
Activated relay proteins
responses
Activated,
unphosphorylated
Fully activated
6 ATP 6 ADP

16. Here’s a more familiar communicator…
Cellular response
Gate open
Gate closes
Signal molecule (ligand)
Gate closed
Ions
Ion channel receptors

17. Transduction
: Cascading reactions (taking several steps) between receptor recognition to cell response
These multistep pathways…
amplify a signal
Provide opportunities to refine regulation

18. Protein Phosphorylation and Dephosphorylation
Each step that adds a phosphate group (remember?)
Adds energy to a molecule, activating it
Adds control and direction to the response to the original signal

19. In this process
Protein kinases = enzymes that add a phosphate (energize) a molecule to another molecule
Phosphatase enzymes then remove the phosphates, recirculating the molecule to be reused

20. Check it out on page 209! A phosphorylation cascade Signal molecule
Active
kinase1
Kinase 2
kinase3
kinase 1 2 3
Inactive
protein
Cellular
response
Receptor P
ATP
ADP PP
Activated relay
molecule i
Phosphorylation cascade P 
A relay molecule
activates protein kinase 1. 1
Kinase + ATP’s P
phos-
Phorylation of
protein kinase 3. 3
protein
phosphatases (PP)
Remove P gp,
kinase is reused 5
Last phosphor. causes 4

21. Small molecules that act as 2nd messengers:1.
Cyclic AMP (cAMP) O –O N O P OH
CH2
NH2
ATP
Ch2
H2O HO
Adenylyl cyclase
Phoshodiesterase
Pyrophosphate
Cyclic AMP
AMP i

22. Many G-proteins trigger the formation of cAMP, a very impt 2ndary messenger…
ATP
GTP
cAMP
Protein
kinase A
response
receptor
G protein
First messenger
The 2nd messenger

23. Ca++ , another second messenger
ATP
CYTOSOL
Ca2+ pump
Nucleus
Key
High [Ca2+]
Low [Ca2+]

24. response to a signal in the cytoplasm:
Glucose (108 molecules)
Glycogen
Active glycogen phosphorylase (106)
Inactive glycogen phosphorylase
Active phosphorylase kinase (105)
Inactive phosphorylase kinase
Inactive protein kinase A
Active protein kinase A (104)
ATP
Cyclic AMP (104)
Active adenylyl cyclase (102)
Inactive adenylyl cyclase
Inactive G protein
Active G protein (102 molecules)
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Transduction
Response
Reception
Value of transduction: AMPLIFICATION

25. May activate transcription
Other pathways
May activate transcription
Reception
Transduction
Response
Gene P
transcription
factor
DNA
Phosphorylation
cascade

26. Fine-Tuning of the Response
Signal pathways with multiple steps…
Can amplify the signal and contribute to the SENSITIVITY of the response