Jaks and STATs are necessary components of cytokine receptor signaling,
regulating growth, survival, differentiation and pathogen resistance. An
example of these pathways is shown for the IL-6 (or gp130) family of receptors.
Jaks (Janus-family tyrosine kinases) constitutively associate with the
receptors. Cytokine binding induces receptor dimerization, activating the
associated Jaks, which phosphorylate the receptor itself. The phosphorylated
receptor then serves as a docking site for the SH2-containing STATs (signal
transducers and activators of transcription), which are latent cytosolic
transcription factors. Receptor-bound STATs are phosphorylated by Jaks,
dissociate from the receptor, dimerize, translocate into the nucleus. Once
in the nucleus, STAT dimers bind specific enhancers, regulating the transcription
of target genes. The SOCS family of proteins (supressor of cytokine signaling)
dampen receptor signaling via homologous or heterologous feedback regulation.
In addition to activating STATs, Jak kinases phosphorylate other signaling/adaptor
proteins, linking Jak signaling to other pathways such as the MAP kinases.
These parallel regulatory pathways are important in shaping the specificity
of cellular responses to various cytokines. Jaks or STATs can also participate
in signaling through other receptor classes, as outlined in the Jak/STAT
Utilization Table
ref1,
ref2,
ref3,
ref4,
ref5
Copyright © 2001-2014 Daniele Focosi.
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