Tbet

Question 1

Tbet:GATA3 interaction - residue

Answer 1

y525 in the transactivation domain must be phosphorylated (by ITK) in order for Tbet to interact with Gata3

Question 2

c-Abl Targets in Tbet

Answer 2

Y219, 265 and 304 (all in the Tbox domain) are all phosphorylated by c-Abl

Question 3

Consequence of c-Abl mediated phosphorylation

Answer 3

If c-Abl can’t phosphorylate Tbet:
no IFNg induction
no TH2 supression

Question 4

Consequence of Tbet-GATA3 interaction

Answer 4

supression of GATA3 and TH2 cytokines via NFkB p65

Question 5

Tbet - T302

Answer 5

Threonine located in the Tbox domain. Phosphorylation is required for supression of IL-2 and TH2 cytokines
T302 is important for interaction with NFAT and subsequent downregulation of IL-4 IL-5 IL13

Question 6

Tbet - K313

Answer 6

Lysine at the end of the Tbox domain. mutation of this residue reduces the ubiqitination mediated tbet degredation.

Question 7

K313 and function of tbet

Answer 7

Mutation of K313 also completely abrogates tbet function, including dna binding, activation of IFNg and supression of IL-2 TH2.

• associates with phosphate of a dna base by H-bond
• GATA3 and NFkB supression is unaffected
• T302 phosphorylation is abrogated as is the NFAT interaction