2) When Signalling Goes Wrong (Cancer)

Question 1

What is a tumour supressor gene?

Answer 1

p53

Question 2

What typeof virus is Rous Sarcoma Virus

Answer 2

Retrovirus, hence why c-src and vsrc and homologous.

Question 3

What is proto-oncogene (cSrc)?

Answer 3

describes cellular version of retroviral transforming gene.

could be mutationally altered to drive cancer.

Question 4

What are the 3 major domains of Src (proto-oncoprotein)?

Answer 4

2 protein-protein domains, SH2 domain on Src.

Question 5

What happens in the SH2 domain?

Answer 5

Interacts with tyrosine phosphorylated residue of C-terminal tail of Src

Question 6

What conformation does Src have when inactive?

Answer 6

folded up tightly

Question 7

What does SH3 mediate?

Answer 7

protein/protein interactions

Question 8

What does SH3 bind to?

Answer 8

bind to stretches of amino acids rich in prolenes.

Question 9

Activation of Src?

Answer 9

P removed from C-terminal tail tyrosine motif. The Src is phosphorylated, active stricture = open

Question 10

v-Src C-terminal difference compared to c-Src?

Answer 10

1) v-Src has lost a key inhibitory C-terminal phosphorylation site –> cant form inactive conformation.
1) cSrc has a C-terminal, control catalytic activity.

Question 11

What is the effect of a mutation in the SH3 domain in vSrc?

Answer 11

interupt the ability of SH3 domain to form compact 3D form.

Question 12

In mutated form of vSrc what can SH3 domain no longer do?

Answer 12

prevent SH3 to prolene rich domains

Question 13

What is the mutated signalling process in Noonan and Tiger syndrome?

Answer 13

MAP-Kinase signalling

Question 14

What kind of receptor is used in Tiger syndrome?

Answer 14

Kinase-linked Receptor (RTK)

Question 15

Does Kinase-linked receptor have an intrinsic tyrosine domain?

Answer 15

YES

Question 16

How is a docking site created on receptor?

Answer 16

The Tyrosine K domain phosphorylates conserved tyrosine residues within the cytoplasmic domain on the receptor.

Question 17

what binds to the docking site?

Answer 17

Adapter molecule Grb2

Question 18

What domain does Gbr2 have that allows it to bind to docking site?

Answer 18

SH2 domain, bind to Tyr phosphorylated motifs.

Question 19

What does Gbr2 recruit and bind to?

Answer 19

Signalling protein sos

Question 20

What activates Ras?

Answer 20

When sos binds to Gbr2

Question 21

How is Ras activated?

Answer 21

Guanine nucleotide exchange factor (GEF)

ADP –> ATP

Question 22

What is the first component activated by Ras in a MAP signalling cascade?

Answer 22

Raf

Question 23

What is the second component activated by Ras in a MAP signalling cascade?

Answer 23

MEK

Question 24

What is the third component activated by Ras in a MAP signalling cascade?

Answer 24

ERK (translocate to nucleus)