Cell Signalling

Question 1

Toolbox

Answer 1

1. ) Receptors
2. ) Intracellular signaling mediatiors
3. ) Target proteins (metabolic enzyme, gene regulatory protein, cytoskeletal protein, exo/endocytosis protein)

Question 2

Receptors

Answer 2

May be named after their natural ligand or a pharmacological one
Types:
Ligand (or voltage) gated ion channels
GPCRs
Enzyme linked (receptor tyrosine kinases)
Nuclear receptors
Metabolic sensing? non-receptor mediated

Question 3

Second Messengers

Answer 3

Signaling depends on concentration.
Generated or released within cell in response to first messenger. Can bind intracell signaling mlcs and regulate their activity.
Ca: enters through ion channels from ECM or intracell stores
cAMP: generated by adenylate cyclase (AC)
IP3: inositol triphosphate, released in phosphate and DAG: diacylglycerol stays in membrane… generated by PL
NO

Question 4

Protein modification

Answer 4

Phosphorylation, acetylation, glycosylation, ubiquitnylation, proteolytic cleavage (of inactive precursors)

Question 5

Protein Protein Binding

Answer 5

Can directly regulate activity/ target a signaling protein to specific locations.
Targeting often involves protein-protein binding.
Can regulate by promoting access to nearby downstream substrates or preventing access to others.

Question 6

GTP/GDP exhange

Answer 6

G-proteins coupled to receptors and in small GTPases.

GTP IS NOT A SECOND MESSENGER b/c signaling through GTP does NOT depend on its concentration

Question 7

When can a signal be terminated?

Answer 7

At any point in a singaling pathway. 
Extracellularly. 
signaled by another signal. 
By enzymes
Some have built in terminators (like ras)

Question 8

Amplification

Answer 8

one upstream activates more than one downstream, can cause further amplification

Question 9

Amplification depends on?

Answer 9

Time it takes to terminate activity of a signaling molecule (beyond the upstream signal?)
How many downstream target mlcs affected?

Question 10

Example of amplification?

Answer 10

Positive feedback loop (sig 1 enhances sig 2 which enhances sig 1)
Often coupled with negative feedback to keep control

Question 11

Network causes?

Answer 11

Cross-talk

Question 12

Coincidence detection

Answer 12

Simultaneous activity (or non-activity) of several receptor types may be needed to get a signaling outcome.
2 may block 1, 2 may be necessary for 1, 2 may modulate 1

Question 13

Why use some connections in a network not others?

Answer 13

1. ) Some may require add’l input
2. ) Signaling protein may not be expressed in that cell
3. ) Wrong location of expression
4. ) Activated but downstream path doesn’t lead to fx.
5. ) Fx. results that we don’t care about

Question 14

Node

Answer 14

Point in a network that receives multiple inputs and/or mulltiple outputs
Calcium is a good example.

Question 15

Modules

Answer 15

Groups of components that fx. together. Often physically associated into complexes.
No rigid defintions.

Question 16

Autocrine

Answer 16

self-stimulation (Receptors on signaling cell)

Question 17

Paracrine

Answer 17

Release signaling mlc that neighboring cells have receptors for

Question 18

Contact-dependent

Answer 18

Signaling mlc not released

Question 19

Endocrine

Answer 19

far away, into blood stream, relatively slow

Question 20

2 major classes of singaling molecules?

Answer 20

1. ) Lipophilic

2. ) Hydrophilic

Question 21

Lipophilic signaling mlcs.

Answer 21

ex: steroid hormones,
yes penetrate mem. 
Receptor can be intra-cellular. 
No cell storage possible. 
Control of release? Only by synthesis
Speed? slow

Question 22

Hydrophilic signaling mlcs

Answer 22

ex: peptides/proteins/AA's
do NOT penetrate mem (makes sense...)
Receptors have to be on cell surface (also duh)
Yes can have cell storage (vesicles)
Control of release? via vesicle release?
Speed? FAST

Question 23

Termination examples

Answer 23

Extracell signaling mlc: degraded, diffuses away
Receptor: desensitization, internalization
2nd messenger: pumped away
Phosphorylation….dephosphorylation
Protein binding: get rid of cmplxs. degrade,

Question 24

Termination mediated by?

Answer 24

Constitutively active terminators (Ca pumps, phosphatases)
Signal induced terminators (phosphatases, GAP)
neg feedback (ca pumps)

most termination events can be modulated by signaling

Question 25

PDE5

Answer 25

Shows cooperativity. Enhanced binding, has catalytic site for breakdown.

Question 26

Consequence of cooperativity?

Answer 26

Activity response is over a smaller concentration gradient (sharper response)