tgfb and fgf

Question 1

tgfβ signal transduction pathway

Answer 1

1. ligand binds to type II receptor
2. type II receptor and type I receptor form a dimer
3. type II receptor activated
4. type II receptor has kinase activity + phosphorylates type I receptor = triggers activation of receptor
5. downstream Smad2 and 3 (if TGFβ receptor) or Smad4 and 5 (if activin/nodal) recruited & phosphorylated by activated receptor
6. Smad4 binds to the other smad proteins –> smad complex formed
7. smad complex = transcription factor. translocates into nucleus and activates TGFβ target genes

Question 2

what are the functions of cross-phosphorylation of RTK

Answer 2

• phosphorylation at kinase domain enhances enzymatic activity
• phosphorylation stabilises RTK in active state
• phosphorylation of tyrosines in cytoplasmic tail of RTK creates docking sites for recruitment of secondary messengers

Question 3

how does Mek activate mapk?

Answer 3

dual phosphorylation of a serine and threonine separated by 1 amino acid

Question 4

FGF receptor structure

Answer 4

single transmembrane domain
3 repeated extracellular Ig-like domains (2 of these are ligand binding sites)
heparin binding site
intracellular kinase activity split into 2 domains

Question 5

DISEASE: achondroplasia

Answer 5

FGF3R mutation

congenital defect of bone formation