Cell Signaling - Bio

 Cells send information to each other. Cells act on received information by changing their
activity to adjust to changing conditions or coordinate their behavior and increase
fitness. Information that is sent and received between cells is in the form of specific
molecules and, occasionally, ions.
 A hormone is a signal that is produced at one location in the body, travels a relatively
long distance, and binds to a receptor in a target cell.
 Organisms also produce a wide array of short-distance chemical messengers that affect
nearby cells, intracellular signals, and chemical signals that are broadcast outside the
body and bind to receptors on different individuals.
 A ligand is any molecule that binds to a receptor.

General Sequence:
 The signaling molecule is released in response to a stimulus from cells, where the signal
is synthesized and stored.
 The messenger travels from source cells to target cells. Chemical messengers are
transported through vascular tissue.
 The signal binds to a receptor protein in a target cell. This binding event is extremely
specific. These receptors are only found in certain cell types.
 When a signal binds to a receptor, the protein changes shape in a way that acts as a
trigger. This structural change of the receptor protein initiates events that lead to the
recipient cell changing its activity.

 In plants and fungi, signaling molecules include the gases ethylene (C2H4) and nitrous
oxide (N2O). Many hormones are relatively small molecules with carbon skeletons that
include ring structures.
 In animals, most of the long-distance chemical messengers belong to one family:
o Amines: Messengers are derived from the amino acids tryptophan and tyrosine.
Some common ones are epinephrine, thyroxin, and melatonin. Most are lipid-
soluble. Some are not.
o Peptides: Small proteins. Some common ones are insulin, oxytocin, and growth
hormones. All are not lipid-soluble.
o Steroids: Major steroid messengers in humans and other mammals are
synthesized from cholesterol and include estrogen, testosterone, and cortisol. All
are lipid-soluble.

 If the signaling molecule is small enough and hydrophobic enough, it is lipid-soluble and
can cross the outer membrane to enter the interior of target cells.
 If the signaling molecule is larger and more hydrophilic, it is not lipid-soluble and cannot
cross the outer membrane of target cells.
 The estrogen receptor is a protein that is found inside the nucleus. When estrogen
diffuses into a cell interior, enters the nucleus, and binds to the receptor, the receptor
complex changes shape in a way that allows it to bind to regulatory DNA sequences.
o The estrogen receptor has three regions: a ligand-binding domain, a flexible
hinge, and a DNA-binding domain.

 An activated receptor only binds to genes with bases capable of interacting with the
particular R-groups on the receptor protein.
 Every lipid-soluble signal binds to a different receptor and regulates the transcription of
different genes.

 When insulin binds to its receptor proteins on the muscle cells and fat cells that function
as its target, those cells then activate carriers that transport glucose out of the blood
and into the cell interior. These target cells store or use the sugar as the blood-sugar
concentration drops to a safe level.
o In the intracellular domain, when insulin is not bound, a group of amino acids
(The mobile loop) is in a position that closes off an active site inside the
structure. When insulin is bound, phosphate groups from ATP are added to the
amino acids in the mobile loop to introduce a negative charge that makes the
loop swing back and reveal the active site. Once it is open, another ATP molecule
diffuses in. Then an intracellular signaling molecule will bind. This will cause the
receptor to catalyze the transfer of a phosphate group from the ATP to the
signaling molecule.
 Signal transduction: converts one type of signal to another type of signal. In the case of
peptide hormones, and some amine hormones, the receptor converts an extracellular
signal to an intracellular signal.
 Kinase: an enzyme that catalyzes the addition of a phosphate group from ATP to another
molecule.

 The intracellular signaling networks that are activated by chemical messengers can lead
to an array of outcomes.
 Phosphorylation acts as an on-off or activation-deactivation switch for many proteins in
a signaling network.
 Cells can integrate information from various chemical messengers because their
signaling networks interact. This is called crosstalk.

 Hormones are present at extremely low levels. Signal amplification occurs with both
lipid-soluble and lipid-insoluble signals.
o When steroid hormones bind to intracellular receptors, they activate the
transcription of many different genes. When a signal-receptor complex binds to
the regulatory sequences for a particular gene, it can promote the production of
many mRNAs. Each mRNA can be translated into protein products often (A
relative handful of estrogen molecules can have an enormous and diverse impact
on target cells, tissues, and organs).
Signal amplification during signal transduction:
 When an activated receptor triggers a series of phosphorylation events, it is called a
phosphorylation cascade. The first kinase that is activated might add phosphate groups
to 10 or more proteins. Those 10 proteins may go on to phosphorylate 10 or more
proteins. The original signal is amplified many times over. The intracellular response is
many times greater than the extracellular signal.
 The response to signal binding is the release of substances that are collectively called
second messengers. A second messenger can either be an ion or a small molecule.
When a receptor binds to a single ligand, it releases many second messengers. Second
messengers can then change the activity of multiple target proteins inside the cell.

In-Class notes:

 Gap junctions between animal cells; Plasmodesmata between plant cells.

 Cell-cell recognition: direct contact between cell surface molecules of two cells.
 Synaptic signaling: neurons release neurotransmitters at a synapse very close to the
target cell.
 Paracrine signaling: local regulators transfer info from cell to cell without a single tissue.
 Endocrine signaling: hormones produce effects away from tissue origin.

 Fight or flight response: a sudden flood of epinephrine (adrenaline) causes changes in

the body (Increased heart rate, pupils dilate, veins dilate, blood-glucose levels increase,
and muscles tense up).
 Signal reception, signal transduction, and cellular response.

 Hormones are secreted by endocrine cells into the blood. Only target cells with
receptors that specifically recognize the hormone will respond to the signal.
  Membrane receptors: G protein-coupled receptors (Split into gamma and beta), receptor
tyrosine kinases (Monomers by themselves, but dimerize (Auto phosphorylation)), and
ion channel receptors (Gated, can open or close).
 Intracellular receptors: Inside the cytoplasm or nucleus. Small or hydrophobic chemical
messengers/ligands can readily cross the membrane and activate responses. An
activated hormone-receptor complex can act as a transcription factor, turning on or off
specific genes.
 Enzyme cascades amplify the cell’s response to the signal. The number of activated
products can be much greater than in the preceding step.

Relay proteins:
1. An activated protein stimulates a relay protein.
2. The relay protein activates a downstream signaling enzyme, which phosphorylates
(Usually K1).
3. Activated K1 phosphorylates and activates multiple downstream signaling enzymes (K2).
4. Activated K2 phosphorylates and activates multiple downstream signaling enzymes (K3).
5. Each activated K3 enzyme phosphorylates multiple downstream targets.

 Inactivation mechanisms are an essential aspect of cell signaling.

o If the concentration of external signaling falls, fewer receptors will be bound.
o Dephosphorylation: protein phosphatases (PP) remove phosphate groups from
proteins. This inactivates proteins.
o Kinases: typically activate proteins.

 Second messengers are small, non-protein, water-soluble molecules/ions spread by

diffusion (cAMP, Ca2+, IP3, and DAG).
o Adenylyl cyclase is an enzyme that converts ATP into Cyclic AMP.
o Ca2+ concentration in the cytosol is normally much lower than outside the cell.
o IP3 and DAG are produced by the cleavage of a type of phospholipid in the
plasma membrane. They work alongside calcium ions.

 DNA damage prevents cell division. Some cancers, however, do not block these damaged
cells from dividing. Some cancers can also mutate a starting signal to force cells to divide
even more than they should.
o RAS is mutated to the “on” state in 20% of all cancers.