Signalling via Receptor Tyrosine Kinases

Question 1

What is the function of the Phosphotyrosine residues on the autophosphorylated RTK?

Answer 1

Serve as “docking sites” for SH2 domain- and PTB domain- containing proteins

Question 2

What is SH2?

Answer 2

Src Homology 2 domain

Question 3

What was the first Tyrosine kinase discovered?

Answer 3

Src protein encoded by a proto-oncogene

Question 4

Where was Src protein discovered?

Answer 4

As the oncogene (v-src) gene of the Rous Sarcoma Virus in cancer studies in chickens

Question 5

What does the SH3 domain bind?

Answer 5

Proline rich motifs

Question 6

What is the mechanism for activation of Ras?

Answer 6

1. Binding of growth factor / hormone causes receptor dimerisation and auto-phosphorylation of tyrosine residues
2. SH2/SH3 containing proteins Sos/GRB2 couples the receptor to inactive Ras
3. Sos causes Ras to exchange GDP for GTP (activated)
4. Sos dissociates
5. Ras signals other proteins such as MAP kinase family (Ser/Thr kinases)
6. Cellular growth genes switched on

Question 7

How does activated Ras signal downsteam?

Answer 7

1. Activated (GTP-bound) Ras binds Raf and activates it
2. Raf (Ser/Thr kinase) initiates a cascade of phosphorylation of MAP/ERK kinases
3. Ser/Thr kinases phosphorylate each other
4. MAP/ERK kinases lead to phosphorylation and regulation of transcription factors (transcriptional regulation)