basic principles of signal transduction

Question 1

What are the major families of cell surface receptors involved in cancer?

Answer 1

RTKs, Cytokine receptors, GPCRs, Frizzled/Wnt receptors, Integrin receptors

Question 2

How do growth factors activate receptor tyrosine kinases (RTKs)?

Answer 2

Ligand binding → receptor dimerisation → transphosphorylation of tyrosine residues

Question 3

What is the role of the juxtamembrane domain in RTK activation?

Answer 3

Helps regulate the activation and autophosphorylation of RTKs

Question 4

What cancer is HER2 overexpression commonly associated with?

Answer 4

Breast cancer (20–30% of cases)

Question 5

How does Trastuzumab (Herceptin) work?

Answer 5

Blocks proteolytic cleavage of HER2 ectodomain

Question 5

What do protein kinases do?

Answer 5

Add phosphate groups to proteins (e.g., on serine, threonine, or tyrosine residues)

Question 6

What do protein phosphatases do?

Answer 6

Remove phosphate groups from proteins

Question 7

What is special about tyrosine phosphorylation?

Answer 7

Rare but leads to major cellular changes (e.g., growth, metabolism)

Question 8

What is Src and what is its function?

Answer 8

Src is a protein tyrosine kinase involved in transformation and signalling

Question 9

What do SH2 domains bind to?

Answer 9

Phosphotyrosine motifs with specific surrounding amino acids

Question 10

What do SH3 domains bind to?

Answer 10

Proline-rich motifs in other proteins

Question 11

What do PH domains bind to?

Answer 11

Phosphoinositides (e.g., PIP3) in the plasma membrane

Question 12

Why are modular domains important in signalling?

Answer 12

They provide specificity and facilitate protein-protein interactions

Question 13

What switches Ras from inactive to active form?

Answer 13

GEFs (e.g., Sos), which replace GDP with GTP

Question 14

What inactivates Ras?

Answer 14

GAPs, by stimulating GTP hydrolysis to GDP

Question 15

What happens when Ras is mutated in cancer?

Answer 15

It becomes permanently active → constant cell proliferation signals

Question 16

What is the main RTK-Ras-MAPK pathway sequence?

Answer 16

RTK → Grb2 → Sos → Ras → Raf → MEK → ERK

Question 17

What is the role of PI3K in signalling?

Answer 17

Converts PIP2 to PIP3 → recruits Akt to membrane → promotes survival/proliferation

Question 18

What does PTEN do?

Answer 18

Reverses PI3K action by converting PIP3 back to PIP2 → tumour suppressor

Question 19

What are the effects of Akt activation?

Answer 19

Promotes growth, survival, metabolism; inhibits apoptosis

Question 20

What is a hallmark of cancer in relation to signalling?

Answer 20

Ability to signal independently of external growth factors

Question 21

How can growth factors themselves act as oncogenes?

Answer 21

when they are overproduced or mutated which can lead to abnormal activation of growth signalling pathways

Example: v-sis (viral homolog of PDGF)

Question 22

What is autocrine signalling in tumour cells?

Answer 22

Tumour cells produce and respond to their own growth factors

Question 23

What RTK is often mutated in gastrointestinal stromal tumours (GISTs)?

Answer 23

c-Kit (gain-of-function mutations)

Question 24

What does Cetuximab do?

Answer 24

Blocks ligand binding to EGFR ectodomain therefore inhibiting the Ras-Raf-MAPK pathway

Question 25

What does Pertuzumab do?

Answer 25

Inhibits HER2 heterodimerisation