1. Janus Kinase/Signal Transducers and
Activators of Transcription (JAK/STAT)
signaling pathway

2. • JAK- Family of cytoplasmic non-receptor
tyrosine kinases which get activated after
the binding of a cytokine to the cell-surface
cytokine receptor.
• STAT- Family of transcription factors that
become activated when one of the tyrosine
residues is phosphorylated by JAK.
• STAT3 dimers then translocate from the
cytoplasm into the nucleus – bind to
Interferon-stimulated Response Elements.
• Cellular responses to dozens of cytokines
and growth factors are mediated by the
evolutionarily conserved.

4. • Ex: Involved in Ig class switching in B Cells
following a response to IL-4 which
phosphorylates STAT6.
• Resistance to viral infection by interferons
mediated through STAT1.
• Trans-phosphorylated JAKs then
phosphorylate downstream substrates,
including both the receptor and the STATs.
• Activated STATs enter the nucleus and
bind as dimers or as more complex
oligomers to specific enhancer sequences in
target genes, thus regulating their
transcription.

5. The JAK/STAT pathway
Harrison D A Cold Spring Harb Perspect Biol
2012;4:a011205
©2012 by Cold Spring Harbor Laboratory Press

6. • Responses include proliferation, differentiation,
migration, apoptosis, and cell survival.
• Essential for numerous developmental and
homeostatic processes, including hematopoiesis,
immune cell development, stem cell
maintenance, organismal growth, and mammary
gland development.
• Human JAK mutations cause numerous diseases,
including SCID, hyper IgE syndrome, certain
leukemias, polycythemia vera, and other
myeloproliferative disorders.
• Small molecular weight cell membrane-permeable
drugs that target this pathways have been
developed for leukemia therapy. (JAK Inhibitors)

7. • Responses include proliferation, differentiation,
migration, apoptosis, and cell survival.
• Essential for numerous developmental and
homeostatic processes, including hematopoiesis,
immune cell development, stem cell
maintenance, organismal growth, and mammary
gland development.
• Human JAK mutations cause numerous diseases,
including SCID, hyper IgE syndrome, certain
leukemias, polycythemia vera, and other
myeloproliferative disorders.
• Small molecular weight cell membrane-permeable
drugs that target this pathways have been
developed for leukemia therapy. (JAK Inhibitors)