Question

Beginning with ligand binding, explain how the JAK-STAT pathway can alter transcription.

Answer 1

Answer-

According to the given question-

JAK-STAT pathway -

• Janus Kinase or JAK are  protein tyrosine kinases which are considered as integral part of cytokines receptor subunits, and responsible for activation of enzyme.
• This is required for initiating the cell signaling cascade which is required for several development such as growth of tissue , embryonic development,,development and differentiation of  haemopoietic cells, also helps in  innate and adaptive immunity as well as signal in inflammatory response.
• When ligand bind with the receptor of trans-membrane then two or more than two receptor which are associated with JAKs comes in close proximity with the help of receptor oligomerization and causes  auto-phosphorylation by stopping the JAK kinase.
• upon activation JAKs leads to phosphorylation of tyrosine residues present in the cytoplasmic domain and form a docking sites for STAT or signal transducers and activators of transcription .
• So they work both function as  cytoplasmic signaling modules as well as work as transcription factors.
• When it binds to the receptor through its SH2 domain then the  STAT work as JAK substrate and this leads to  Phosphorylation of SH2 domain tyrosine residue present between SH2 domain and trans-activation domain which are at C-terminal.This leads to  formation of dimer of STAT and later it was stabilized through interaction between the phosphotyrosine and SH2 domain.
• When Dimer formation takes place then it leads to  translocation towards the nucleus and coming in close contact with nucleus the dimers of STAT attaches to palindromic sequences present in the promoter regions of target genes and this leads to initiation of transcription.