IL-7 signaling pathway (WP205)
Interleukin-7 (IL-7) was discovered in the year 1988 as a factor that enhanced the growth of murine B-cell precursors in bone marrow culture system. It was also known as lymphopoietin 1and pre-B cell factor. IL-7 plays an important role in the development of B and T cells in mouse and T cells in humans. It is also essential for mature and naive T-cell's survival and proliferation. Human IL-7 gene maps to chromosome 8 and is about 72kb in length. The protein encoded by this gene is 177 amino acids in length with a molecular weight of 20 kDa. The active form of IL-7 in humans is a glycoprotein of 25 kDa. In humans IL-7 has been shown to be produced from intestinal epithelial cells, keratinocytes , hepatic tissues, peripheral blood dendritic cells, follicular dendritic cells, endothelial cells, smooth muscle cells and fibroblasts. The IL-7 receptor consists of IL-7 receptor alpha chain (IL-7RÎ±) and a common gamma chain (Î³c). The gamma chain is also shared by IL-2, IL-4, IL-9, IL-15 and IL-21 receptors. The signaling pathways activated upon IL-7 binding to the receptor complex are JAK-STAT, PI-3 kinase and Src kinase pathways. JAK3, a protein tyrosine kinase is constitutively associated with the carboxy-terminal region of the gamma chain. Studies in mice lacking JAK3 have shown that it is required for transducing Î³c dependent signals. Mutations in JAK3 and Î³c have been shown to be associated with the autosomal recessive form of T-B + SCID. JAK1, another protein tyrosine kinase is associated with IL-7RÎ± chain and is activated upon IL-7 binding. JAK1 deficient mice shows severely impaired thymic development and no hematopoietic colony formation in response to IL-7. IL-7 would first bind to IL-7RÎ± and then associates with the gamma chain, bringing their intracellular domains bearing JAK1 and JAK3 together. JAK3 phosphorylates IL-7RÎ± chain creating docking sites for the transcription factors, STAT1, STAT3, and STAT5. JAK1 and JAK3 phosphorylate these STAT molecules and induces their dimerization and translocation to the nucleus where they activate specific target genes. PTK2B, a protein tyrosine kinase has been shown to be associated with JAK1 and plays an important role in the survival of thymocyte cell line. The enzymatic activity and its phosphorylation are highly induced by IL-7. PI-3 kinase pathway is also activated by IL-7 and this pathway is essential for the survival and proliferation of human T cell precursors. PI-3 kinase interacts with IL-7RÎ± upon IL-7 stimulation and activates its downstream target, AKT and its activation is mediated by Î³c. AKT in turn activates GSK3 beta and Bad, the death protein. Survival of pro T-cell survival by regulating Bad via PI3 kinase/AKT pathway is mediated by IL-7. IL-7 also mediates the downregulation of cyclin-dependent kinase inhibitor 1B through the PI-3 kinase pathway and this effect is required for cell proliferation. IL-7 also induces the phosphorylation of a Src kinase family member, Fyn which is constitutively associated with IL7RA. In addition, IL-7 induces phosphorylation of MAPK family members including MAPK1 and MAPK3. Please access this pathway at [http://www.netpath.org/netslim/IL_7_pathway.html NetSlim] database. If you use this pathway, please cite following paper: Kandasamy, K., Mohan, S. S., Raju, R., Keerthikumar, S., Kumar, G. S. S., Venugopal, A. K., Telikicherla, D., Navarro, J. D., Mathivanan, S., Pecquet, C., Gollapudi, S. K., Tattikota, S. G., Mohan, S., Padhukasahasram, H., Subbannayya, Y., Goel, R., Jacob, H. K. C., Zhong, J., Sekhar, R., Nanjappa, V., Balakrishnan, L., Subbaiah, R., Ramachandra, Y. L., Rahiman, B. A., Prasad, T. S. K., Lin, J., Houtman, J. C. D., Desiderio, S., Renauld, J., Constantinescu, S. N., Ohara, O., Hirano, T., Kubo, M., Singh, S., Khatri, P., Draghici, S., Bader, G. D., Sander, C., Leonard, W. J. and Pandey, A. (2010). NetPath: A public resource of curated signal transduction pathways. Genome Biology. 11:R3. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP205 CPTAC Assay Portal]
AuthorsAkhilesh Pandey , Kristina Hanspers , Martijn Van Iersel , Alex Pico , NetPath , Christine Chichester , Zahra Roudbari , Egon Willighagen , Martina Summer-Kutmon , Lauren J. Dupuis , and Eric Weitz
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- DNA methylation of ARHGAP30 is negatively associated with ARHGAP30 expression in lung adenocarcinoma, which reduces tumor immunity and is detrimental to patient survival (2021).
- RNA-Seq analysis of seasonal and individual variation in blood transcriptomes of healthy managed bottlenose dolphins (2016).
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Pathway OntologyInterleukin mediated signaling pathway interleukin-7 signaling pathway
|IL-7 stimulation induces the phosphorylation of PTK2B in human chondrocytes.
|IL-7 stimulation induces phosphorylation and nuclear transport of STAT5A in human peripheral blood T lymphoblasts.
|IL-7 stimulation leads to phosphorylation of STAT5B in CD8 T cells and human peripheral blood T lymphoblasts respectively.
|IL-7 stimulation induces tyrosine phosphorylation of the kinase JAK1 in human thymocytes
|The common gamma chain augments IL-7 binding affinity and internalization of IL-7, which may explain the defects in X-linked severe combined immunodeficiency.
|IL7 stimulation induces increased phosphorylation of STAT3 in normal human chondrocytes and T lymphoblasts.
|IL7 stimulation induces increased phosphorylation of JAK3 in normal human chondrocytes and thymocytes.
|IL-7 stimulation leads to tyrosine phosphorylation of STAT1 in human CD4 T cells and murine YT-5 cells