Signal Transduction 1/2

Question 1

What type of molecules are signals, what are the different types

Answer 1

• signals are ligands
• they can be agonists (stimulate pathways) or antagonists (inhibit pathways)

Question 2

describe the mechanism of the direct contact signal

Answer 2

target cell has a receptor, which connects to a ligand that is attached to the signalling cell

Question 3

describe the mechanism of gap junction signal, where are they used

Answer 3

• small signalling molecules and ions
• electrical synapses use gap junctions between neurons
• connexins between different neurons join and form gap junctions

Question 4

describe the mechanism of the autocrine signal

Answer 4

• target cell makes its own ligand and expresses it outside the cell, then it bids receptors on the same cell
• self stimulation (ligands can’t travel far because they have a very short half life)

Question 5

what are eicosanoids

Answer 5

• self stimulating growth signals derived from fatty acids

Question 6

how does autocrine signalling relate to cancer

Answer 6

• if a cell is able to produce its own growth factors then it control its own growth through autocrine signalling
• often found in cancers

Question 7

describe the mechanism for paracrine signalling

Answer 7

• ligand induces respond in target cell that is close to the signalling cell

Question 8

how does a neuromuscular junction work in terms of signalling

Answer 8

• nerve impulse travels down neuron
• stimulates vesicle movement to membrane until they bind
• Ach released and binds to ion exchange channels
• channels open, sodium moves in and potassium moves out ]
• muscle twitches and acetylcholinesterase degrades Ach

Question 9

describe the mechanism of endocrine signalling

Answer 9

• ligand is produces by endocrine cells and is carried into the blood until it reaches distant target cells
• these ligands = hormones

Question 10

what are the extra examples of signalling

Answer 10

• odours and taste
• light
• gas
• pheromone

Question 11

how is signalling specificity driven by cell-type specific expression

Answer 11

• some receptors are only present on certain cells
• molecules downstream of the receptor are only present in certain cells

Question 12

how does cell-type specific expression occur?

Answer 12

genes are turned on/ off by activators or repressors with enhancer or silencer control elements

Question 13

how signalling specificity driven by affinity?

Answer 13

• the precise molecular complementarity between ligand and receptor

Question 14

how do you calculate association rate, what are the units of the constant

Answer 14

k+ X receptor concentration X ligand concentration
k = M^-1 S^-1

Question 15

hoe do you calculate the dissociation rate, what are the units of the constant

Answer 15

k X receptor ligand complex concentration
k = s^-1

Question 16

what are the units of Keq (the equilibrium constant)

Answer 16

M^-1

Question 17

how are signals amplified

Answer 17

• amplified by enzyme cascades e.g. a receptor/ enzyme associated with a receptor is activated, which then activates the next round of enzymes

Question 18

why does desensitisation to signals occur?

Answer 18

• when a signal is present continuously
• you only regain sensitivity after signal falls below threshold level again

Question 19

describe the process of EGFR signalling

Answer 19

1. EGF binds EGFR and activates it, so it changes configuration then it’s phosphorylated
2. recruits adaptor molecule then Ras, then Raf
3. growth signal amplified MAPK
4. desensitisation by dephosphorylation of EGFR
5. cross-talk from other pathways affects MAPK conc., which enters nucleus and changes gene expression

Question 20

what are the normal blood glucose levels and what hormones (and in which places) do we use to maintain normal BG levels

Answer 20

• 4.5 mM
• insulin and glucagon (pancreatic)
• epinephrine and cortisol (adrenal)

Question 21

where is insulin and glucagon produced

Answer 21

• both produced in the pancreas
• cells at the end of the duct are called acini
• between acinar cells, smaller a/b cells found which are the producers

Question 22

how do receptor sub-units get to the membrane

Answer 22

• after translation they enter ER
• associate into dimers
• transported to cell surface by golgi
• cleaved into a (on the outside) and b (on the inside) sub-units
• displayed as trans-membrane proteins at plasma membrane

Question 23

how does insulin alter gene expression/ act as a growth factor

Answer 23

• binds in between a sub-units
• alters shape and brings them closer together
• b sub-units phosphorylate each other (results in IR activation)
• IRS-1 becomes activated, then becomes captured by Grb 2 and sos
• this complex captures Ras and activates it
• this activates Raf which activates MEK which activates ERK

Question 24

how does insulin change blood sugar concentration

Answer 24

• insulin binds receptor
• activates receptor through shape change and auto trans phosphorylation
• IRS-1 phosphorylates
• activates PI3 kinase
• converts membrane proteins and results in activation of PKB

Question 25

what are the functions of insulin?

Answer 25

- it is a growth factor at high concentration, as it stimulates changes in gene expression - it is a glucose regulator at lower concentrations, as it upregulates glucose entry into cells and glycogen production

Question 26

how can insulin take part in more than 1 pathway

Answer 26

- because there is a common intermediate step (activation of IRS-1) - one pathway is Ras independent (altered metabolism) and the other is Ras dependent (growth signals)

Question 27

how do we turn off the Ras independent pathway

Answer 27

- PTEN removes a phosphate from PIP3 and allow it to become PIP2

Question 28

what is the difference between Type I and Type II diabetes

Answer 28

Type 1 is diabetes mellitus, failure to produce insulin Type 2 is non-insulin-dependent diabetes mellitus , failure to respond to insulin

Question 29

how does insulin prevent high blood sugar

Answer 29

- binding of insulin results in activated PKB - stimulates GLT4 movement from internal vesicles to plasma membrane to uptake glucose - PKB mediates conversion of excess glucose to glycogen and triacyl glycerides

Question 30

who was the first to provide the concept of BMI? What were the ranges ?

Answer 30

1835 Adolphe Jaques Quetelet BMI>30 obese 25-30 overweight under 25 = normal

Question 31

what are the mechanisms we use to deal with excess calories

Answer 31

- excess fuel converted to fat stored in adipose tissue - increased locomotor activity/ more exercise - conversion of excess fuel to heat (thermogenesis)

Question 32

what is the lipostat theory (1953)

Answer 32

- when we synthesise to much fat we would receive a signal telling us to stop eating (not real)

Question 33

evidence to support lipostat theory

Answer 33

- mice injected with live virus that make them leptin deficient and they got fat and became diabetic (not insulin related)

Question 34

what is the role of leptin

Answer 34

- released by adipose tissue and binds with receptors in hypothalamus, stimulates release of a-MSH r=that modulates nervous transmission - makes us eat less and

Question 35

mechanism of leptin

Answer 35

- binds extracellular ligand of Lep-R, makes it dimerise - this creates binding sites for JAK, which is soluble and phosphorylates Lep-R - STATs 3, 5 and 6 bind, then are phosphorylated by JAK - STATs dimerise and enter nucleus and are ACTIVE TFs - precursor for a-MSH made (tells us to stop eating)