Biosignalling

Question 1

Ligands and receptors interact in which way with each other?

Answer 1

Non covalently

Question 2

What are the 6 features of signal transduction?

Answer 2

1. Amplification
2. Modularity
3. Desensitization/Adaption
4. Specificity
5. Integration
6. Localization

Question 3

What is integration?

Answer 3

Ability of the system to receive multiple signals and produce a unified response

Question 4

What is specificity?

Answer 4

Receptors have specific ligands

Question 5

How can a desensitized system become resensitized?

Answer 5

When the stimulus falls below a certain threshold

Question 6

What is an effector?

Answer 6

Selectively binds to protein and regulates its activity, act as ligands, can increase/decrease enzyme activity

Question 7

How many transmembrane alpha helices do GCPR’s have?

Answer 7

7

Question 8

What are the 3 essential components of GPCR’s?

Answer 8

1. Plasma membrane protein receptor with 7 alpha helices
2. G protein (cycles between active/inactive)
3. Effector Enzyme/ion channel regulated by G protein

Question 9

What is the 1st messenger for GPCR’s?

Answer 9

Extracellular ligand

Question 10

When is a G protein active?

Answer 10

When it’s GTP bound

Question 11

When G protein attaches to GTP, does it stay on the receptor?

Answer 11

No, dissociates, then binds to effector

Question 12

What is the 2nd messenger in GCPR’s?

Answer 12

Cytosolic metabolite/inorganic ion

Question 13

What are the ligands for andrenergic receptors? (GCPR’s)

Answer 13

Epinephrine

Question 14

What is an agonist?

Answer 14

Natural ligand, produce effect of natural ligands

Question 15

What is an antagonist?

Answer 15

Bind receptor without effect, block agonists

Question 16

What is the stimulatory G protein? (Gs)

Answer 16

Activates the effector

Question 17

In andrenergic receptors, what is the Gs?

Answer 17

Gsalpha

Question 18

What activates adenylyl cyclase in andrenergic receptors?

Answer 18

Gsalpha

Question 19

What catalyzes the formation of cAMP in andrenergic receptors?

Answer 19

Adenylyl Cyclase

Question 20

What does cAMP activate?

Answer 20

Protein Kinase A

Question 21

When concentration of cAMP is low, is PKA active or inactive?

Answer 21

Inactive

Question 22

When PKA is active, what is the cAMP concentration?

Answer 22

High

Question 23

How does adenylyl cyclase create cAMP?

Answer 23

Removes 2 p’s off of ATP to create cAMP

Question 24

What are the 3 ways signals can be terminated? (andrenergic receptors)

Answer 24

1. Epinephrine concentration goes below threshold
2. Hydrolysis of GTP bound to G alpha-end cAMP production
3. cAMP is hydrolyzed to 5’AMP by cyclic nucleotide phosphodiesterase

Question 25

What does cyclic nucleotide phosphodiesterase do?

Answer 25

Hydrolyze cAMP to 5'AMP

Question 26

What are GAPs?

Answer 26

GTPase Activator Proteins: Stimulate GTPase activity=more rapid inactivation of G protein

Question 27

What are RGS?

Answer 27

Regulators of G protein signalling

Question 28

What are the 4 classes of Galpha?

Answer 28

1. Gsalpha: Stimulates AC 2. Gialpha: inhibits AC 3. Gqalpha: Stimulates PLC 4. G12/betagamma: Regulate actin cytoskeleton

Question 29

What happens when Gi binds to AC?

Answer 29

Hormones that induce Gi binding inhibit AC

Question 30

How are andreneric receptors desensitized?

Answer 30

Protein kinase phophorylates receptor on intracellular domain that normally interacts with Gs

Question 31

What does BARK do?

Answer 31

Binding of epinephrine triggers dissociation of Gsby from Gsalpha-Gsby recuits BARK=phosphorylates Ser residues near COOH

Question 32

How are BARK and B-arrestin involved in GPCRs?

Answer 32

Desensitization- 1. Binding of epinephrine triggers dissociation of Gsby from Gsalpha-Gsby recuits BARK=phosphorylates Ser residues near COOH 2. Phosphorylation creates binding site for B-arrestin-blocks receptor sites that interact with Gs 3. Receptor taken into cell via endocytosis-dephosphorylated=resensitized

Question 33

How does PKA contribute in desensitization of GPCRs?

Answer 33

PKA activated by high cAMP phosphorylates and activates BARK

Question 34

What are AKAPS?

Answer 34

A Kinase binding Protein-localize PKA

Question 35

GPCR coupled with PLC uses what kind of signalling?

Answer 35

IP3 and Ca2+

Question 36

What does PLC do?

Answer 36

Catalyzes cleavage of membrane PIP2 to and DAG. Activated by Gs.

Question 37

Which 2nd messenger opens Ca2+ channels?

Answer 37

IP3

Question 38

What does high cytosolic Ca2+ concentration do?

Answer 38

Trigger activation of PKC

Question 39

What is the extracellular domain of TKR usually made of?

Answer 39

Cys, Leu

Question 40

What are the 2 pathways TKR signals with?

Answer 40

MAPK (rigrrmet) and PIP3

Question 41

Where is the enzyme active site on TKRs?

Answer 41

Cytoplasmic face-protein kinase

Question 42

What does riggRRmet stand for? (Insulin receptor)

Answer 42

``` r- Receptor i- IRS g- grb2 R- RAS R- RAF m-MEK e-ERK t- Target ```

Question 43

What does ERK do? (RTK)

Answer 43

Enters nucleus and phosphorylates transcription factors, activating them

Question 44

Which molecule does PIP3 path branch at from MAPK?

Answer 44

Grb 2 is not the only protein IRS1 associates with-also PI3K

Question 45

What does PI3K do?

Answer 45

1. Binds to active IRS1 | 2. Phosphorylates PIP2 to PIP3 using ATP

Question 46

What are the 2 paths in insulin PIP3 signalling?

Answer 46

A: Activated PKB phophorylated GSK3=inactive, can't inactive GS=glycogen synthesis accelerated B: PKB stimulates GLUT4 to move to plasma membrane and open= more glucose uptake

Question 47

What does GSK3 do?

Answer 47

Phophorylated glycogen synthase (GS), making it inactive.

Question 48

Phosphorylated IRS1 provides binding sites for which 2 adaptor proteins?

Answer 48

Grb2 and PI3K

Question 49

What does PIP3 do in insulin signalling?

Answer 49

Allows PKB to dock, which is then phosphorylated by PDK1

Question 50

When GSK3 is phosphorylated, is it inactive or active?

Answer 50

Inactive.

Question 51

Kinases most commonly phosphorylate which amino acids?

Answer 51

Ser, Thr, Tyr

Question 52

What does polarized mean?

Answer 52

Cell is in resting membrane potential state.

Question 53

What does depolarized mean? What is the ion movement?

Answer 53

Inside becomes more positive, Na and Ca rush in

Question 54

What does hyperpolarized mean? What is the ion movement?

Answer 54

inside becomes more negative, Cl- and K+ rush out

Question 55

What is the ion movement when a signal travels through an axon?

Answer 55

Na+in, K+ out

Question 56

Why does Cl- move against the concentration gradient?

Answer 56

Moving due to electrical gradient instead.

Question 57

What acts as the 2nd messenger in neurons?

Answer 57

Ca2+

Question 58

When Ca concentration in neurons increases, what happens?

Answer 58

Triggers release of acetylcholine into synaptic cleft

Question 59

What happens when acetylcholine binds to its ligand gated receptor?

Answer 59

Opens channel, allowing cations (Na and Ca) to enter

Question 60

What percentage of nuclear receptors are not inside the cell?

Answer 60

5-10%

Question 61

Why is signal transduction for nuclear receptors usually slow?

Answer 61

Ligand must be hydrophobic and cross cell membrane via diffusion.

Question 62

How do nuclear receptor ligands travel around the body?

Answer 62

Bound to carrier proteins.

Question 63

What happens when the ligand binds to a nuclear receptor?

Answer 63

Receptor dimerizes with other receptor, and binds to hormone response elements (HREs)-then receptor attracts corepressors/coactivators