Signaling I

Question 0

Why can’t these signals get through the membrane? What happens instead?

Answer 0

They are soluble, hydrophilic molecules so can’t get through PM.
They communicate to inside cell trough transmembrane receptors

Question 1

What can cells sense from their environment?

Answer 1

Nutrients, toxins, heat, light
Pheromones (from other individuals)
Signaling molecules (from same individual)

These signaling molecules control metabolism, growth, migration, differentiation

Question 2

What kinds of receptors are there for cell signaling?

Answer 2

Cell surface receptors for hydrophilic molecules (proteins).
Intracellular receptors: receptor goes into nucleus (hydrophobic like steroids)

Question 3

What are the different schemes for signing?

Answer 3

1. Endocrine (insulin): act at distance
2. Paracrine (infection): signal targets nearby cells
3. Autocrine (cancer): signaling targets same cell.
4. Contact dependent (development): membrane attached signal targets adjacent cell.

Question 4

What are the different responses cells can have?

Answer 4

Survival, grow&divide, differentiate, die

Depends on combination of signals

Question 5

What is signal transduction?

Answer 5

Conversion of one type of signal (extracellular) to another type of signal (intracellular).

Question 6

What are the functions of signal transduction?

Answer 6

Propagate signal in cell
Amplify signal thru 2nd messengers
Integrate all signals to time response
Activate response by distribution

Question 7

How can the speed of response from signal differ?

Answer 7

Fast: simply alter function of protein through phosphorylation.

Slow: alter gene expression by making long term changes like transcription or translation.

Both lead to altered cell behavior

Question 8

How is receptor interaction with signaling molecules controlled?

Answer 8

Through affinity of ligand to receptor given by kd.
There’s an equilibrium of rs↔️r+s. (Bound vs unbound).
The lower the kd the higher the affinity.

Question 9

What are the different signal transduction pathways in metazoa?

Answer 9

1. Gpcr
2. RTK
3. Notch
4. Tgf-beta
5. Cytokines (jak/stat)
6. Wnt
7. Hedgehog
8. Nuclear hormone receptor
9. Integrins
10. Toll
11. Hippo

Question 10

How is gpcr targeted?

Answer 10

Histamine!

Question 11

What connects gpcr from outside to inside the cell?

Answer 11

Heterotrimeric G protein (alpha is bound to gtp once ligand binds to gpcr) and g alpha is turned on and separates from beta and gamma subunits.

Question 12

How does gpcr activate phospholipase C? Give mech.

Answer 12

Activated g alpha activates plc
Plc cleaves PIP2 to get IP3
IP3 causes ca2+ release from ER
DAG and ca2+ activate pkc to phosphorylate proteins downstream.

Question 13

How do antihistamines work and what is an example?

Answer 13

Antihistamines block the gpcr signal of the histamine H1 receptor ( block ligand binding site). This blocks the downstream signaling that ultimately leads to itchiness or sneezing or other allergic responses.