2-3 Signaling I

Question 1

How does a cell receive a signal, and what happens as a result?

Answer 1

• Signaling molecule (ligand) binds noncovalently to a cellular protein (receptor) →
• Conformational change in the receptor →
• Δ activity (if receptor = enzyme) or Δ affinity for another molecule (if receptor lacks enzymatic activity)
• Messages that can’t enter cells directly are bound by receptors at the surface and the information is passed on through internally generated second messengers

Question 2

How does signal amplification occur?

Answer 2

When a ligand binds to a receptor molecule, there is often a large increase in the conc. of some intracellular second messenger molecule, which amplifies the signal.

Question 3

Why is signal amplification important?

Answer 3

• Fewer receptors and signaling molecules are needed to get the cell to respond
• Shorter response time
• Second messengers can spread throughout cell (and even to neighboring cells through gap junctions)

Question 4

How is signal concentration controlled?

Answer 4

Signal concentration is often controlled by feedback loops that regulate how fast the signaling molecule is produced, whereas the rate of removal (the turnover rate or half-life) is usually (but not always) constant for any one signaling molecule.

Rapid changes in signal strength require a short signal half-life (a fast rate of removal through clearance or degradation).

Question 5

What are some factors in the cellular response to signals?

Answer 5

• Signaling molecule conc.
• # of available receptors
• Receptor affinity for the signaling molecule
• Expression of tissue- or cell-type specific second messenger systems

Question 6

What is target cell adaptation with regard to signaling?

Answer 6

Adaptation is a change in the cell’s responsiveness to a specific signal concentration. It may be accomplished by changing:

• # of available receptors: fewer receptors → less sensitive cell; more receptors → more sensitive cell
• receptor affinity for ligand: lower affinity receptor → less sensitive cell
• response sensitivity of second messenger pathways to receptor activation: smaller response to receptor occupancy → less sensitive cell

Question 7

What is signal integration?

Answer 7

• Each cell integrates information from many signals
• One signal can bind to different receptors in different cells, or the same type of receptor can activate different second messengers in different cells
• Two signaling molecules may act through the same second messenger, so that a boost in the concentration of one signal makes the cell more sensitive to the other one

Question 8

What are some types of external signal delivery, and what are their relative affinities?

Answer 8

• Endocrine signals are carried through the bloodstream. High affinity (provided in low concentrations, have to travel a distance)
• Paracrine signals are mediated to local cells. Intermediate affinity
• Autocrine signals secreted by a cell that binds to receptors on the same cell. Low affinity (provided in high concentrations)

Question 9

What are some classes of signaling molecules?

Answer 9

• Small, rapidly diffusible molecules such as NO and CO pass into cells and alter enzyme activity directly. Very short half-lives (sec)
• Hydrophobic steroids, retinoids, and thyroid hormones are usu. carried by binding proteins in the blood and pass directly thru cell membranes to bind to cytoplasmic/nuclear receptors. Relatively long half-lives (hrs-days)
• Hydrophobic eicosinoids are phospholipid-derived. Prostaglandins, prostacyclins, leukotrienes and thromboxanes. Usu. autocrine. Typical functions: inflammatory responses and blood clotting. Bind to surface receptors, have short half-lives

Question 10

How do nuclear receptors act as a primary signal transduction mechanism?

Answer 10

Nuclear receptors activate gene transcription.

• Diversity/specificity is provided by a family of related receptor proteins (each with DNA binding and hormone binding domains)
• Each DNA binding domain recognizes a specific DNA sequence, but actual receptor binding usu. requires dimerization
• Many form heterodimers with other TFs that contribute to binding specificity
• Nuclear translocation induced by hormone binding is common

Question 11

How do hydrophilic signals act as primary signal transduction mechanisms?

Answer 11

1. Ion channels: voltage-gated, mechanically gated, or gated by extracellular (1° signals) or intracellular ligands (second messengers). Selectivity varies
2. G-protein-linked receptors act via direct assoc. w/ one of several trimeric G-proteins (GTPases that act as activation/inhibitory switches)
3. The most common enzyme-linked receptors stimulate membrane-associated tyrosine-specific protein kinases but lack enzymatic activity of their own
4. Catalytic receptors have cytoplasmic domains that act as enzymes when a ligand binds to the extracellular domain. Serine/threonine kinases, tyrosine kinases, phosphatases, guanylate cyclases