Signal Transduction Pathways in Development: the JAK/STAT Pathway

Abstract

The Janus Kinase (JAK)/signal transducer and achivator of transcription (STAT) pathway is activated not only by various cytokines such as interferon and interleukin, but also by many growth factors. This pathway plays a crucial role in the signal transduction of these factors.

Keywords: Cytokine; JAK; STAT; SOCS; PIAS; PTP

Figure 1.

Domain organization of JAK kinases and STAT proteins. (a) Seven JAK homology (JH) domains are located in the C‐ to N‐terminus direction. JH1 is the tyrosine kinase domain and JH2 is the noncatalytic pseudokinase domain. The roles of the other JH domains are not well understood. (b) STAT proteins possess a leucine zipper (LZ), DNA binding domain (DBD), SH3, SH2 and transactivation domain (TAD) in the direction from the N‐ to the C‐terminus. SH2 and the tyrosine residue between SH2 and TAD are essential for the activation.

Figure 2.

Schematic representation of STAT activation. JAKs are associated with cytokine receptors before stimulation. (a) Upon ligand binding, receptors are oligomerized, which leads to the activation of JAKs due to autophosphorylation. The JAKs then phosphorylate the receptors. (b) STAT monomers bind to the receptors and are phosphorylated on tyrosine residue by JAKs. (c) Phosphorylated STATs are released from the receptors, dimerize and translocate into the nucleus.

Figure 3.

Inhibition mechanisms of the SSI/SOCS/CIS family. Both SSI‐1/SOCS1 and CIS1 are induced by activated STATs and inhibit the activation of STATs by suppressing JAK activity (SSI‐1/SOCS1), or by preventing the binding of STATs to receptors (CIS1).

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Naka, Tetsuji, and Ohkawara, Tomoharu(Apr 2006) Signal Transduction Pathways in Development: the JAK/STAT Pathway. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0004188]