JAK-STAT signaling

Question 1

What happens with STAT following activation by JAK?

Answer 1

After activation, STAT dissociates from the receptor to form dimers and enter the nucleus to control gene expression (as transcription factors)

Question 2

How do STAT proteins get phosphorylated in the JAK/STAT pathway?

Answer 2

Binding of a cytokine causes two ciytokine receptors to dimerize. Associated JAKs on the recepotrs are brought together so that they can phosphorylate eachotheron tyrosines to become fully activated. After this, they phosphorylate te receptors to generate binding sites for the SH2 domains of STAT proteins. JAKs also phosphorylate STAT proteins.

Question 3

Describe the mechanism that has a negative effect on the activity of the JAK-STAT pathway.

Answer 3

STAT dimers can activate genes that encode inhibitory proteins that help shut off the response. These proteins bind and inactivate phosphorylated JAKs and their associated receptors. Or bind to STAT dimers and prevent them from binding to DNA targets. (these negative feedback mechanisms are not enough to turn off the response). Inactivation of the activated JAKs and STATs requires dephosphorylation by protein tyrosine phosphatases.

Question 4

Where are STAT protein located and why are they referred to as latent transcription regulators?

Answer 4

STAT proteins are located in the cytosol, and are referred to as latent transcription regulators because they migrate into the nucleus and regulate gene transcription only after they are activated.