JAKSTATSignale

JAKSTATSignale, commonly written as JAK-STAT signaling, denotes a signal transduction pathway that transmits information from extracellular cytokines and growth factors to the nucleus via a JAK-STAT cascade. The core components are the Janus kinases (JAK1-3 and TYK2) bound to type I and II cytokine receptors and the STAT family transcription factors (STAT1-6).

Activation occurs when ligands bind receptors, causing receptor dimerization and JAK activation; JAKs phosphorylate receptor cytoplasmic domains creating docking sites for STATs; JAKs phosphorylate STATs; phosphorylated STATs dimerize and translocate to the nucleus to regulate gene expression.

Cytokines such as IL-6, IL-2, IFN-γ, and growth factors utilize JAK-STAT signaling; specifics include IL-6 family signals via gp130 using JAK1/JAK2/TYK2; IFN signals via JAK1/JAK2; IL-2 signals mainly via JAK1/JAK3; JAK3 is largely restricted to hematopoietic cells.

Physiological roles of JAK-STAT signaling include hematopoiesis, immune responses, inflammation, and development. Dysregulation or mutations (for example, JAK2 V617F) contribute to myeloproliferative neoplasms and inflammatory diseases; aberrant STAT activation is associated with various cancers.

Therapeutic modulation includes JAK inhibitors (jakinibs) such as ruxolitinib (JAK1/2), baricitinib (JAK1/2), and tofacitinib (JAK1/3). These agents reduce signaling in inflammatory diseases and myeloproliferative disorders but may cause immunosuppression and infection risk. Negative regulation is provided by SOCS proteins, SHP phosphatases (SHP-1, SHP-2), and PIAS proteins.