JAK-STAT signaling cascade ; GO:0007259
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- 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).
- Activated JAK proteins phosphorylate the receptor.
- STAT proteins are recruited to the phosphorylated receptor.
- JAK proteins phosphorylate the STAT proteins.
- Phosphorylated STAT proteins dimerize (hetero- or homo-) and translocate to the nucleus.
- 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?
- With the receptor, which activates JAK?
- 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.