1. Ch. 14 Part 6
Cell Signaling

2. Cell Signaling
How living organisms control and coordinate their bodies
Based on getting a message from one place to another place
Outside the cell to inside the cell
Inside the cell to outside the cell
Two Major mechanisms of signaling
Secretion of Chemical Signals
Direct cell-cell contact
Ex. Embryonic development and lymphocyte attacks
Cell membrane plays big role in cell signaling
Contains protein “receptors”
Stimulus (signal) receptor  transmission of mission “signal transduction” target (effector) response

4. Signals Signals Single molecules are usually very small and diverse
Produced by body
Hormones and neurotransmitters
Stimuli
Light, drugs, pheromones
Single molecules are usually very small and diverse
Hydrophobic, insoluble molecules get across membrane no problem
Steroids
Ex. oestrogen
Most signal molecules are water soluble
need to attach to cell membrane receptors to relay signal
Distance travelled by molecules can be small or short
Signals can be electrical (nervous system) or chemical (endocrine system) events

5. Signal Receptor in Cell Membrane
Transmembrane proteins
“Receptor”
Specific shape
Only on certain cells
When signal molecule attaches to receptor on the outside of the cell:
conformational changes occur to protein that spans the membrane
Signal from outside is “transduced”
Changes to the shape of the receptor protein initiates a “domino” effect
Transmits the signal to another protein inside the cell
G-Proteins (alpha, beta, gamma)
G proteins activate another molecule/protein

6. How Receptors Alter the Activity of a Cell
Activating the release of second messengers
Opening an ion channel
Changes membrane potential
Ex. Nicotine-accepting acetylcholine receptors
Acting directly as a membrane-bound enzyme
Ex. Insulin receptor
Acting as an intracellular receptor when the initial signal passes straight through the cell surface membrane
Ex. Oestrogen receptor
Found in nucleus and directly controls gene expression when combined with hydrophobic oestrogen hormone

7. G Proteins Protein Family Respond diverse stimuli
G Protein Coupled Receptors (GPCRs)
Transmembrane protein
Guanine nucleotide-binding proteins
Intracellular proteins
Alpha, beta, and gamma
Respond diverse stimuli
light, compounds, bioactive lipids, cytokines, hormones, and neurotransmitters
Activation puts specific G proteins into play
Changes in G-protein structure alters the activity of enzymatic signaling pathways
they bind the guanine nucleotides GDP and GTP (that is the “switch” that relays the signal from outside)

8. Receptor G Protein receives the signal molecule
Changes shape to activated alpha G-protein inside the cell membrane
“switch”
Activated G protein (now with GTP) moves to stimulate another receptor molecule that releases the “second messenger” molecule
“amplifies” original signal
Key feature of cell signaling

9. Second Messenger Molecule
Amplifies original signal
Usually activates enzyme that activates other enzymes
Increases amplification of original signal
“signaling cascade”
Sequence of events triggered by G protein
Final enzyme activated brings about required change in cell metabolism
Common Second messagner is cAMP
Cyclic Adenosine Monophosphate
Made from ATP
Binds to Kinase Enzymes

10. Kinases
Enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation)
Phosphorylation usually results in a functional change of the target protein (substrate) by:
changing enzyme activity
cellular location
association with other proteins

11. How Second messengers Work

12. Possible Signaling Pathways in Cells