Cell Signaling
Why Do Cells Need Signals?
- To respond to a changing environment
- A cellular response to the environment can be critical for survival
- Example: Glucose signals yeast cells to increase glucose transporters and enzymes allowing efficient uptake and use of glucose
Cell Signaling Requirements
- Signaling Molecule
- Large hydrophilic molecules
- Small hydrophobic molecules
- Hormones
- Receptor
- Transmembrane
- Cytosolic
- Nucleoplasm
Signals Relayed Between Cells
Direct intercellular signaling: Cell junctions allow signaling molecules to pass from one cell
to another.
Contact-dependent signaling: Molecules bound to the surface of cells serve as signals to
cells coming in contact with them.
Autocrine signaling: Cells secrete signaling molecules that bind to their own cell surface or similar neighboring cells.
Paracrine signaling: signal does not affect originating cell, but does influence nearby cells
Endocrine signaling: signals called hormones travel long distances and are usually longer lasting in effect
Three Stages of Cell Signaling
- Receptor activation: signaling molecule binds to receptor
- Signal transduction: activated receptor stimulates a sequence of changes
- a signal transduction pathway
- Cellular response
- Different responses possible
- Change enzyme activity
- Change function of structural proteins
- Change gene expression
Cell Signaling: Responding to the Outside World
- Interpreting extracellular signals via proteins that span their plasma membrane called receptors
- Receptors are comprised of extracellular and intracellular domains
- The extracellular domain relays information about the outside world to the intracellular domain
- The intracellular domain then interacts with other intracellular signaling proteins
- These intracellular signaling proteins further relay the message to one or more effector proteins
- Effector proteins mediate the appropriate response
- Same receptor molecule can interact with many intracellular relay systems at the same time so same signal and same receptor => different effects in different cells
- Same relay system many act on many different intracellular targets
- By changing the conformation of a receptor, signals lead to a response inside the cell.
Reception
- A receptor
- Has to have an endogenous ligand
- Has to bind it with high affinity (strength)
- Has to recognize the biologically active ligand from other similar molecules (specificity)
- Has to produce the biological response
- All the conditions have to be met
Signal Transduction Pathway
- First messenger: signals binding to the cell surface
- Many signal transduction pathways lead to production of second messengers
- Second messengers: relay signals inside cells
- Examples:
- cAMP
- Ca²⁺
- Diacylglycerol (DAG) and inositol triphosphate (IP₃)
Signal Transduction via cAMP
- Cyclic adenosine monophosphate
- Signal binding to GPCR activates G protein to bind GTP, causing dissociation, freeing α subunit
- α subunit binds to adenylyl cyclase enzyme, stimulating synthesis of cAMP
- cAMP then activates protein kinase A (PKA)
- Activated catalytic PKA subunits phosphorylate specific cellular proteins
- PKA targets include
- enzymes
- structural proteins
- transcription factors
- When signaling molecules no longer produced, eventually effects of PKA are reversed
- cAMP has two advantages
- Signal amplification: binding of signal to one receptor can cause the synthesis of many cAMP molecules that activate PKA, and each PKA can phosphorylate many proteins
- Speed: in one experiment a substantial amount of cAMP was made within 20 seconds after addition of signal
Signal transduction via DAG and IP3
- Another way for an activated G protein to activate a signal transduction pathway
- α subunit activates phospholipase c
- Phospholipase C cleaves plasma membrane phospholipid PIP₂ producing diacylglycerol (DAG) and inositol triphosphate (IP3)
- Ca2+ channels in ER open, causing Ca²⁺ influx
- Ca2+ exerts a variety of effects on cell behavior