Controlling cells

Question 1

What is cellular signalling important for?

Answer 1

• Communication between cells

- Critical for normal development and function

Question 2

What is the general mechanism of cellular signalling?

Answer 2

1) Reception of a signal
2) Transduction of signal
3) Cellular response

Question 3

What 5 crucial functions do signaling cascades perform?

Answer 3

1) Transduce
- Signal into molecular form that can stimulate a response

2) Relay
- Signal from point of reception to point of action in the cell

3) Ampliy
- The received signal

4) Distribute
- The signal to influence several responses in parallel

5) Modulation
- By other signals
- Can happen at any step

Question 4

Examples of direct communication between cells?

Answer 4

1) Gap junction s

2) Interaction of cell surface molecules

Question 5

Examples of local communication between cells?

Answer 5

1) Paracrine signalling
2) Synaptic signalling
3) Hormonal signalling

Question 6

How do hydrophobic molecules act as signalling molecules?

Give an example

Answer 6

• Pass through the membrane
• Directly acitvate intracellular receptos in the cytoplasm or nucleus of the target cell
  eg. steroid hormones

Question 7

How do hydrophillic molecules act as signalling molecules?

Give an example

Answer 7

• Can’t cross the membrane
• Rely on membrane receptors
  eg. NO, chemically unstable, uncharged gas

Question 8

What are the 3 categories of enzyme-linked receptors?

Answer 8

1) Receptor tyrosine kinase
2) Cytokine receptors
3) TGT- beta type receptors

Question 9

What are the ligands of receptor tyrosine kinases?

Answer 9

Soluble or membrane-bound peptide or protein hormones

Question 10

What do mutant forms of RTK do?

Answer 10

Send proliferative signals to cells in the absence of a signal

Question 11

What do RTKs do?

Answer 11

1) Autophosphorylate themselves
2) Phosphorylate tyrosine residues on target proteins and themselves
3) Stimulates assembly of a signalling complex where other proteins can ‘dock’

Question 12

How are the RTK complexes disassembled?

Answer 12

By protein tyrosine phosphatases

Question 13

What do RTKs activate?

Answer 13

1) Activate Ras (G protein)

2) Activate the PI-3 kinase-Akt pathway

Question 14

What happens when Ras is activated?

Answer 14

Ras activates a the MAP-kinase cascade

• MAP-kkk
• MAP-kk
• MAP-k

Question 15

What happens when the PI-3 kinase-Akt pathway is activated?

Answer 15

Akt serves as a suvival signal for the cell and stimulates cell growth

Question 16

What are cytokines?

Answer 16

Small, secreted proteins which control growth and differentiation of many types of tissues

Question 17

What happens when a cytokine receptor is activated?

Answer 17

it signals to the nucleus in a direct pathway

Question 18

What do TGF beta receptors do?

Answer 18

Exert anti-proliferative signals to cells

Question 19

What happens if there is a mutation in the TGF beta pathway?

Answer 19

• Contribute to malignancy
• Often associates with pancreatic cancers
• But also implicated in colon, liver and gastric tumours

Question 20

What is the OFF state of WNT signalling?

Answer 20

1) Beta-catenin is associated with E-cadherin
2) Targeted phosphorylation of B-catenin by CDK1 and GSK3beta leads to ubiquitination
3) Ubiquitination leads to breakdown of B-catenin

Question 21

What is the ON state in WNT signalling?

Answer 21

1) WNT ligand binds frizzled receptors
2) LRP5/6 brought to WNT/frizzled complex
3) This complex activates dishevelled (Dvl)
4) Dvl displaces GSK3beta, preventing Beta-catenin destruction
5) Beta-catenin is free to be translocated to nucleus, turns on genes by displacing co-repressors from TCF/LEF1 (on DNA)

Question 22

5 ways to inactivate receptor signalling?

Answer 22

1) Receptos sequestation
2) Receptor downregulation
3) Receptor inactivation
4) Inactivatio of signalling protein
5) Production of inhibitory protein

Question 23

What ligands can bind to TGF-beta receptors?

Answer 23

NODAL

ActivinA

TGFb

Question 24

Which SMADs do the TGF-b receptors phosphorylate?

Answer 24

2 or 3

Question 25

What ligands can bind to BMP receptors?

Answer 25

GDF3

NOGGIN

Question 26

Which SMADs do BMP receptors phosphorylate?

Answer 26

1, 5 or 8

Question 27

Which co-SMAD are all SMADs competing for and what does this mean?

Answer 27

SMAD4

There must be a balance of TGF-beta and BMP signalling

Question 28

What type of signalling is WNT and BMP?

Answer 28

Long range

Question 29

What type of signalling is NOTCH?

Answer 29

Short range - works between adjacent cells