Signal transduction

Question 1

Agonist ligands

Answer 1

Stimulate pathways

Question 2

Antagonist ligands

Answer 2

Inhibit pathways (drugs)

Question 3

Gap junction signalling

Answer 3

Exchange of small molecules + ions
Metabolic reactions

Question 4

Paracrine signalling

Answer 4

Ligand induces response in target cell close to signalling cells

Question 5

Autocrine signalling

Answer 5

Ligand induces response in signalling cell (SELF-STIMULATION)

Question 6

Endocrine signalling

Answer 6

Ligand produced + carried in blood (hormone)
Response in distant target cells

Question 7

Insulin signalling

Answer 7

1. Insulin binds IR
2. Activated IR phosphorylates IRS-1
3. IRS-1 binds to Grb2 (which is bound to Sos)
4. Sos acts as a GEF (guanine nucleotide exchange factor) to convert inactive Ras-GDP → active Ras-GTP
5. Ras recruits + activates Raf
6. Raf phosphorylates MEK
7. MEK phosphorylates MAPK
8. MAPK enters nucleus to alter gene expression

Question 8

Glucose regulation

Answer 8

1. IRS recruiters + activates PI-3K (kinase)
2. PI-3K phosphorylates (PIP2 -> PIP3)
3. PIP3 acts as secondary messenger - recruited PDK1
4. PDK1 activates PKB (protein kinase B/Akt)
5. Akt phosphorylates targets

Question 9

PTEN

Answer 9

Removes phosphate from PIP3 (-> PIP2)
No recruitment of PDK1 + PKB

Question 10

Leptin

Answer 10

1. Dimerised Lep R
2. Creates site for recruitment of JAK (kinase)
3. JAK phosphorylates LepR
4. LepR recruits STATS (Signal transducer + activated of translation - 3,5, 6)
5. JAK phosphorylates fat STATS
6. STATS dimerise + expose NLS
7. STATS enter nucleus as transcription factors
8. α-MSH precursor processed -> α-MSH
9. α-MSH signals brain to stop eating

Question 11

EPO signalling

Answer 11

1. JAK-STAT pathway using STAT5
2. JAK autophosphorylation - EPO signalling can access Ras dependent pathway

Question 12

GPCR structure

Answer 12

Barrel
x7 TM helices

Question 13

Heterotrimeric G protein

Answer 13

Gα - binds GDP (inactive) or GTP (active)
Gβ, Gγ - form Gβγ upon activation

Question 14

GPCR desensitisation - arrestin

Answer 14

Binds to this phosphorylated receptor blocking further interaction with G proteins

Question 15

Gs

Answer 15

Stimulates adenylate cyclase

Question 16

Gi

Answer 16

Inhibits adenylate cyclase

Question 17

Type 1 error

Answer 17

Believing falsehood

Question 18

Type 2 error

Answer 18

Rejecting truth

Question 19

Cortisol

Answer 19

Long term
Increases blood sugar

Question 20

Andregenic receptors

Answer 20

Binds epinephrine
α - inhibits insulin secretion
β - triggers glucagon secretion

Question 21

β andregernic GPCR receptor

Answer 21

Coupled to Gs:
Gαs activated - stimulates adenylate cyclase
Gβs inhibits

Question 22

α andregernic GPCR receptor

Answer 22

Coupled to Gi:
Gαi activated - inhibits adenylate cyclase
Gβγi activates MAPK

Question 23

Cholera toxin

Answer 23

1. CTxA1 linked to GxA2 by disulphide bnd
2. Disulphide bond broken by PDI (between CTxA2 - GxA2)
3. BIP (binding protein) keeps CTxA1 soluble
4. CTxA1 dislocates across ER in unfolded form
5. CTxA1 refolds

Question 24

Light capture isomerisation

Answer 24

1. Light absorption causes trans isomerisation around C12 + 13 of retinal
2. N of key lysine moves
3. Activation of rhodopsin

Question 25

Light capture - GPCR

Answer 25

1. Changed confirmation of GPCR (rhodopsin -> activates meterhodopsin II) 2. Meterhodopsin stimulates nucelotide change on α subunit of transducin 3. cGMP PDE stimulated - removes cGMP from ion channels 4. cGMP -> GMP 5. Na⁺/Ca²⁺ ion channels close causing hyperpolarisation

Question 26

Na⁺/Ca²⁺ ion channels

Answer 26

1. Light closes channels decreasing [Ca] 2. Activates granulate cyclase - to increase cGMP

Question 27

Sidenafil citrate

Answer 27

Inhibits cGMP phosphodiesterase (PDE-5 + 6) Blue tinged vision

Question 28

Nitric oxide

Answer 28

Activates granulate cyclase

Question 29

Calcium + nitric oxide synthase (NOS)

Answer 29

1. High [Ca] activates NOS 2. NOS converts arginine -> citruline + NO (unstable) 3. NO -> nitrites + nitrates by paracrine signalling 4. NO activates guanylate cyclase by binding haem group

Question 30

Protein kinase G

Answer 30

Phosphorylates myosin light chain Dilation of blood vessels

Question 31

Oestrogen E1

Answer 31

Oestrone - menopause

Question 32

Oestrogen E2

Answer 32

Oestradiol - reproductive years

Question 33

Oestrogen E3

Answer 33

Oestril - pregnancy

Question 34

Oestrogen E4

Answer 34

Oestretol

Question 35

Oestrogen receptor (ER)

Answer 35

N terminal DNA binding domain C terminal hormone binding domain Stored as complex with Hsp90 (chaperone)

Question 36

Oestrogen signalling

Answer 36

1. Oestrogen binds ER 2. Er released from Hsp90 3. ER-oestrogen complex enters nucleus + binds oestrogen response elements 4. Oestrogen responsive genes transcribed 5. Oestrogen binds GPCR 6. EGF release via Ca 7. Stimulation of MAPK via Gbr2

Question 37

Tamoxifen

Answer 37

Breast cancer treatment ER antagonist Cells remain in G0/G1