4.3

Question 1

What is the role of modular domains in RTK signalling?

Answer 1

They mediate protein-protein/phospholipid interactions for signal propagation.

Question 2

What is a common feature of signalling proteins?

Answer 2

They often consist of multiple domains (SH2, SH3, PH, PTB) and motifs (pY, PXXP, PIP3).

Question 3

Give an example of a protein with multiple modules and motifs.

Answer 3

IRS1 (PTB, PH domains; multiple tyrosines).

Question 4

What is the role of IRS1 in signalling?

Answer 4

It is a docking protein phosphorylated by RTKs, serving as a platform for further signalling.

Question 5

What RTK phosphorylates IRS1?

Answer 5

The insulin receptor.

Question 6

What motif on the insulin receptor recruits IRS1?

Answer 6

Y960 motif.

Question 7

What proteins bind to phosphorylated IRS1?

Answer 7

Grb2, PI3K, Nck.

Question 8

What type of ligand usually activates this pathway?

Ras/Raf/MAPK Pathway

Answer 8

Mitogens (growth factors).

Question 9

List the main cascade of kinases in this pathway.

Answer 9

Ras → Raf (MAPKKK) → MEK (MAPKK) → ERK (MAPK).

Question 10

What are key outcomes of this pathway?

Answer 10

Cell proliferation, differentiation, and growth.

Question 11

What activates Ras in this pathway?

Ras/Raf/MAPK Pathway

Answer 11

GTP binding after recruitment by adaptor proteins like Grb2.

Question 12

What does PI3K do in this pathway?

Answer 12

Converts PIP2 to PIP3 at the plasma membrane.

Question 13

What domain in proteins like Akt binds to PIP3?

Answer 13

PH domain.

Question 14

What proteins are downstream of Akt?

Answer 14

mTOR, S6K, TSC1/2, RHEB.

Question 15

What is the effect of this pathway on the cell?

PI3K/Akt Pathway

Answer 15

Promotes survival, protein synthesis, and cell growth.

Question 16

What phosphatase opposes PI3K action?

Answer 16

PTEN – dephosphorylates PIP3 back to PIP2.

Question 17

What are JAKs and how are they activated?

Answer 17

Non-receptor tyrosine kinases activated by dimerisation of cytokine receptors.

Question 18

What is the main downstream target of JAKs?

Answer 18

STAT proteins.

Question 19

What happens to STATs after phosphorylation?

Answer 19

They dimerise and translocate to the nucleus.

Question 20

What biological processes does JAK/STAT regulate?

Answer 20

Cell survival, immune response, transcription.

Question 21

What cytokine receptor is commonly used as a model in this pathway?

📡 JAK/STAT Pathway

Answer 21

gp130 (e.g., in IL-6 signalling).

Question 22

What regulates JAK/STAT to prevent overactivation?

Answer 22

SOCS proteins (Suppressor of Cytokine Signalling).

Question 23

What diseases are linked to JAK/STAT dysfunction?

Answer 23

Cancers (haematological, liver), autoimmune diseases.

Question 24

What is the gp130∆STAT mouse model?

Answer 24

Lacks STAT-binding sites on gp130 → reduced fibrosis.

Question 25

What is the gp130757F mouse model?

Answer 25

Mutation at Y757 enhances STAT signalling → increased fibrosis.

Question 26

What is c-Src?

Answer 26

A non-receptor tyrosine kinase with SH3, SH2, and kinase domains.

Question 27

What keeps c-Src inactive?

Answer 27

3 mechanisms: Switch (Y416 unphosphorylated), Clamp (SH3 binds PXXP linker), Latch (pY527 binds SH2).

Question 28

How is c-Src activated?

Answer 28

Dephosphorylation of Y527, release of SH3 from linker, phosphorylation of Y416.

Question 29

What types of receptors can activate c-Src?

Answer 29

RTKs, GPCRs, cytokine receptors.

Question 30

What processes does active c-Src regulate?

Answer 30

Proliferation, survival, motility, differentiation.

Question 31

What happens if c-Src is constitutively active?

Answer 31

Oncogenic transformation → cancer.

Question 32

What causes tyrosine kinase dysregulation in cancer?

Answer 32

Overexpression, gain-of-function mutations, loss of regulatory controls.

Question 33

What are examples of oncogenic tyrosine kinases?

Answer 33

EGFR/HER (overexpressed in tumours), BCR-Abl (leukaemia).

Question 34

What distinguishes RTKs and non-RTKs in activation?

Answer 34

RTKs = ligand-dependent; non-RTKs (e.g., c-Src) = regulated by conformation and upstream signals.

Question 35

What viral oncogenes are derived from non-RTKs?

Answer 35

v-Src, v-Abl.

Question 36

What is the correct sequence in the Ras/Raf/MAPK pathway?

Answer 36

Ras → Raf → MEK → MAPK (Answer: C).

Question 37

What is PI3K’s role in the PI3K/Akt pathway?

Answer 37

Phosphorylates PIP2 into PIP3 (Answer: B).

Question 38

What activates the JAK/STAT pathway?

Answer 38

Ligand binding to cytokine receptors → JAK activation (Answer: C).