1. Signals and Responses
Cell Communication

2. Simple Communication Stimulatory Inhibitory
Activate some sort of behavior, activity, gene expression etc.
Shut off behavior, activity, gene expression etc.

3. Origin of Cell Signaling
Began as way for single celled organisms to “communicate” with each other
E.g. when it gets crowded bacteria can send signals to shut off reproduction

4. Purpose of Signaling in Multi-Cellular Organisms
Coordinate cellular actions
E.g. when frightened you release epinephrine fight or flight responses

5. Distance of Communication
Direct contact
Local communication
Long distance

6. Example of Direct Connection
Antigen- presenting White blood cell directly contacts helper T cells
Activates immune responses

7. Example of Local Regulation
Neurotransmitters
Serotonin, dopamine etc. carry signals from one part of brain to others
Only affects cells in local area

8. Example of Long Distance Signaling
Hormones
Released from endocrine glands and travel through blood
Affect many target cells throughout the body

9. Three Stages of Cell Signaling
Reception
Detection of Chemical Signal
Transduction
Conversion of the signal form
Response
Cell responds in any number of ways

10. Signal Molecules are Ligands
A cellular receptor binds a ligand, a molecule that matches the receptor’s shape
Lock and Key – each receptor fits only 1 ligand
Reception

11. Signal Receptors Most signal molecules can’t pass through the membrane
So they bind to a protein in the membrane
Usually large, transmembrane proteins, which change shape
Reception

12. 1. G-Protein-Linked Receptors
A receptor protein connects to a G-protein, which is normally inactive and bound to GDP
When the signal ligand binds to the receptor, the receptor becomes “activated” and changes shape
Reception

13. This shape change causes the receptor bind to the G-protein
Causes a GTP molecule to displace the GDP, activating the G-protein
Reception

14. The active G-protein binds to an enzyme, switching on the enzyme
The enzyme's activity begins the process of signal-transduction
Reception

15. G Proteins and Medicine
Diabetes, blindness, allergies, depression and some cancers are believed to come from dysfunctional G proteins
Up to 60% of medicines used influence G- Protein Pathways
Reception

16. 2. Tyrosine-Kinase Receptors
Two Transmembrane Helices
Part of receptor is enzyme
Two subunits, when in-active are separate
Reception

17. Activating T-K Receptors
Ligand binding causes the two subunits to come together
This activates the enzyme, phosphorylating Tyrosines
Receptor then activates proteins
Reception

18. Tyrosine-Kinase Triggers Multiple Pathways at Once
A single dimer (two polypeptide protein) can activate more than ten proteins
Growth factors are examples of Tyrosine- Kinase receptors
Growth factors stimulate many cellular responses at once
Important in Cell Reproduction
Reception

19. 3. Ion-Channel Receptors
Ligand bonding induces change in structure of receptor
Open or close channels that let specific ions into or out of the cell
Changes electrochemical gradient, triggering cellular response
Reception

20. 4. Intracellular Receptors
Some chemical signals are hydrophobic lipids or small molecules that can pass through the plasma membrane
Often bind to receptors in the cytosol or nucleus
Examples include steroids, Nitric Oxide (NO) and some other small molecules
Alter gene expression
Reception

21. Signal-Transduction Pathways
Relay signals from receptors to cellular responses
Usually multi-step pathway
Signal amplification – large numbers of molecules can be activated from a small number of signals
More opportunities for regulation
Transduction

22. Transduction

23. Second Messengers Small, non-protein, hydrophilic molecules or ions
Spread through cell by diffusion
Spread the signal from G-protein receptors and Tyrosine-Kinase receptors
cAMP
Calcium Ions
Transduction

24. Cyclic AMP
Adenyl Cyclase converts ATP to cAMP after receptor binds signal molecule
cAMP activates protein kinase A
Protein Kinase A phosphorylates proteins (adds a phosphate group)
Transduction

25. Protein Phosphorylation
Very common mechanism for regulating protein activity
A protein kinase is an enzyme that phosphorylates a proteins
1% of our genes are for these enzymes
Many kinases act upon another kinase, creating a phosphorylation cascade
Protein phosphatases remove the phosphate group, turning off the signal
Transduction

26. Transduction

27. Calcium Ions
DAG,PIP and IP3 simulate release of Ca++ ions from the Endoplasmic Reticulum
Ca binds to proteins and activates them
Can also activate a phosphorylation cascade
Transduction

28. Transduction

29. Cellular Response May Occur in Cytoplasm
Rearrangement of skeleton
Opening or closing of channel
Effect on metabolism
Enzyme activation
May affect expression of genes in the cell's nucleus
Not all genes are “turned on”
Signals can turn genes on or off
i.e. growth factors
Response

30. Response Specificity
A signal may have different response in different cells
This depends on the receptors, second messengers and proteins present in the cell
Ex. Adrenaline causes different reactions in different organs
Response

31. Importance of Cell Signaling
Diseases result from incorrect signaling
Drugs often target signaling mechanisms
Poisons and pesticides often target signaling pathways