JAK-STAT signaling cascade ; GO:0007259

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  1. Ligand-binding to the cell-surface receptor introduces a conformational change in the receptor, which brings the JAK proteins into close proximity with eachother. The close JAK proteins trans-phosphorylate eachother (may also autophosphorylate).
  2. Activated JAK proteins phosphorylate the receptor.
  3. STAT proteins are recruited to the phosphorylated receptor.
  4. JAK proteins phosphorylate the STAT proteins.
  5. Phosphorylated STAT proteins dimerize (hetero- or homo-) and translocate to the nucleus.
  6. STAT dimers enter the nucleus (through importin) and activate transcription of their target genes.

JAK-STAT SIGNALING: Outstanding Questions

where does JAK-STAT signaling begin?

  1. With the receptor, which activates JAK?
  2. With JAK activity (phosphorylating the receptor and downstream STAT proteins)?

E.g. is the receptor functioning in the cascade, or upstream of the cascade?



 GO:0007261: JAK-induced STAT protein dimerization
The formation of a dimer of two STAT proteins (Signal Transducers and Activators of Transcription) following their activation by members of the janus activated kinase (JAK) family of tyrosine kinases.