What is STAT3 pathway?
In the canonical STAT3 signaling pathway, activation of cell surface growth factor and cytokine receptors induces specific tyrosine phosphorylation (small red circles) of receptor chains to create docking sites for the recruitment of latent cytoplasmic STAT3 (dark gray geometries), which contain SH-2 domains (shown as …
How does the JAK STAT pathway work?
The JAK/STAT pathway regulates embryonic development and is involved in the control of processes such as stem cell maintenance, haematopoiesis and the inflammatory response. The pathway transduces signals from cytokines, interleukins and growth factors that act through a number of transmembrane receptor families.
What does the JAK pathway do?
The JAK-STAT pathway in cytokine receptor signalling can activate STATs, which can bind to DNA and allow the transcription of genes involved in immune cell division, survival, activation and recruitment. For example, STAT1 can enable the transcription of genes which inhibit cell division and stimulate inflammation.
What activates STAT5?
STAT5 can be activated by various hormones and cytokines, including IFNα, IFNβ, IL-3, GM-CSF, thrombopoietin, and erythropoietin [10,62,91,92]. Interestingly, CrkL has been shown to form a complex with STAT5 under these conditions as well.
How is JAK activated?
Activated JAK is characterised by phosphorylation of activation loop residues within its kinase domain (encircled P; middle). Activated JAKs phosphorylate tyrosines within the receptor intracellular region to enable recruitment and phosphorylation of the principal downstream effectors, the STATs.
What genes does STAT3 activate?
On activation, STAT3 dimerizes and translocates to the nucleus, where it acts by epigenetic remodeling to regulate transcription of target genes such as MnSOD, ERα, survivin, Bcl-2, and Bcl-xL.
What genes does STAT5 regulate?
Activation of the Immune System STAT5 regulates the transcription of the Il4 gene by binding two DNase I hypersensitivity sites, HSII and HSIII, and regulating accessibility to the gene (Zhu et al., 2003; Cote-Sierra et al., 2004).
How are JAK1 and STAT3 activated in NSCLC cells?
In NSCLC cells with acquired resistance to targeted drugs, we observed activation of the IL6-cytokine pathway and STAT3 along with epithelial-to-mesenchymal transition (EMT) features.
How does the JAK-STAT signaling pathway affect the immune system?
Given that many JAKs are associated with cytokine receptors, the JAK-STAT signalling pathway plays a major role in cytokine receptor signalling. Since cytokines are substances produced by immune cells that can alter the activity of neighbouring cells, the effects of JAK-STAT signalling are often more highly seen in cells of the immune system.
Is the JAK1 / STAT3 axis a therapeutic target?
Our data suggest that the OSMRs/JAK1/STAT3 axis contributes to resistance to targeted drugs in oncogene-driven NSCLC cells, implying that this pathway could be a therapeutic target. Mol Cancer Ther; 16 (10); 2234-45. ©2017 AACR .
How does JAK-STAT integrate with the MAPK / ERK pathway?
JAK-STAT signalling can also integrate with the MAPK/ERK pathway. Firstly, a protein important for MAPK/ERK signalling, called Grb2, has an SH2 domain, and therefore it can bind to receptors phosphorylated by JAKs (in a similar way to PI3K). Grb2 then functions to allow the MAPK/ERK pathway to progress.