Cell Signaling

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

Signaling Molecule * Large hydrophilic molecules * Small hydrophobic molecules * Hormones
Receptor * Transmembrane * Cytosolic * Nucleoplasm

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

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

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.

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

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)

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

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