JAK/STAT

Question 1

Ligands in this pathway include: (5)

Answer 1

• Growth hormones
• Some growth factors
• Most interleukins and interferons
• Prolactin
• Erythropoietin

Question 2

4 types of human STAT mutants

Answer 2

AR complete
AR partial
AD
AD gain of STAT1 activity

Question 3

Which STAT is associated with oncogenic effect?

Answer 3

STAT3

Question 4

Noonan syndrome

Answer 4

Stunted growth and immunodeficiency

50% have GOF mutations in SHP2 phosphatase

Question 5

Mutating STAT 3 leads to…..

Answer 5

Spontaneous dimerization via disulphide bridge formation leading to constitutive activation, immortalisation of fibroblasts and tumour formation in mice

Question 6

What sort of mutation is associated with myeloproliferative diseases?

Answer 6

Activating mutations of JAK2, especially V617F

Question 7

Pegvisomant

Answer 7

GH analogue used to treat acromegaly
G120R substitution in GH interferes with binding to second receptor
Modifications at site 1 enhance binding and increase inhibitory activity
Addition of PEG molecules to lysine side chains increases half life

Question 8

What causes acromegaly?

Answer 8

Almost always a GH secreting tumour

Question 9

What are the 4 treatment options for acromegaly?

Answer 9

Surgery and/or radiation
Octreotide (somatostatin analogue)-inhibits GH secretion
Dopamine antagonists
Pegvisomant