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-7Rα) and a common gamma chain (γc). 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 γc dependent signals. Mutations in JAK3 and γc have been shown to be associated with the autosomal recessive form of T-B + SCID. JAK1, another protein tyrosine kinase is associated with IL-7Rα 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-7Rα and then associates with the gamma chain, bringing their intracellular domains bearing JAK1 and JAK3 together. JAK3 phosphorylates IL-7Rα 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-7Rα upon IL-7 stimulation and activates its downstream target, AKT and its activation is mediated by γc. 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. <i>Genome Biology</i>. 11:R3. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP205 CPTAC Assay Portal] bec 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 IL-7 stimulates the tyrosine phophorylation of FYN in pre-B cells and cultured embryonic neurons. Stimulation of IL-7 receptor induces the phosphorylation of PYK2 in D1 murine embryonic thymocytes and human chondrocytes. IL-7 stimulates the phosphorylation of AKT1 at Ser 473 in TAIL7 and BaF-3 cells FOXO inactivation by PI3K-AKT pathway contributes to the downregulation of p27KIP1 IL-7 stimulates the tyrosine phosphorylation of STAT5B and its interaction with IL-7 receptor phosphorylated at Tyr 449 in peripheral blood lymphocytes. IL-7 stimulates the interaction of STAT3 with IL-7R phosphorylated at Tyr 449 in peripheral blood lymphocytes. IL-7 stimulates the binding of intracellular domain of IL7 receptor alpha chain to JAK1 followed by tyrosine phosphorylation of STAT5A at Tyr 694 in various cell lines such as D1 cells, murine CT6 cells and NAG8/7 cells. IL-7 stimulates the phosphorylation of MEK1 at Ser 218 and MEK2 at Ser 222 in TAIL-7 cells. IL-7 stimulates the phosphorylation and heterodimerisation of STAT5A and 5B and its translocation from cytoplasm to the nucleus in human peripheral blood lymphocytes. IL-7 stimulation leads to tyrosine phosphorylation of JAK3 and its association with the common gamma chain. IL-7 stimulates the tyrosine phosphorylation of STAT5A and its interaction with IL-7 receptor phosphorylated at Tyr 449 in peripheral blood lymphocytes. IL-7 stimulates the interaction of cytoplasmic tail of IL-7 receptor with phosphorylated Fyn in human pre B-cell line Nalm-6 which in turn activates phosphatidylinositol 3-kinase. IL-7 stimulates the activation of NFkB pathway and the expression of NFkB responsive genes in primary T lymphocytes. IL-7 stimulates the phosphorylation of ERK1 and ERK2 in TAIL-7, murine pBCR and YT5 cells. IL-7 stimulation induces the tyrosine phosphorylation of STAT5A and STAT5B leading to their heterodimerisation in human peripheral blood T lymphoblasts. IL-7 binds with the recombinant IL-7 receptor alpha chain with the same affinity as the native receptor in COS-7 cells. IL-7 stimulates the phosphorylation and activation of AKT1 which phosphorylates GSK3-beta at Ser 9 in TAIL7 cells. PYK2 is constitutively associated with JAK1 and the stimulation of IL-7 receptor induces the phosphorylation of PYK2 in D1 cells. IL-7 stimulates the interaction of the p85 subunit of PI3-kinase with the IL7 receptor alpha chain via SH2 domain, to a motif based upon a phosphorylated tyrosine 449 residue in the cytoplasmic tail of IL7R in murine pre B-cell 8-18 cells and human thymocytes. JAK1 constitutively associates with the cytoplasmic domain of IL-7R alpha chain in human peripheral blood leukocytes and CD4 T cells. 20067622 PubMed NetPath: a public resource of curated signal transduction pathways. Genome Biol 2010 Kandasamy K Mohan SS Raju R Keerthikumar S Kumar GS Venugopal AK Telikicherla D Navarro JD Mathivanan S Pecquet C Gollapudi SK Tattikota SG Mohan S Padhukasahasram H Subbannayya Y Goel R Jacob HK Zhong J Sekhar R Nanjappa V Balakrishnan L Subbaiah R Ramachandra YL Rahiman BA Prasad TS Lin JX Houtman JC Desiderio S Renauld JC Constantinescu SN Ohara O Hirano T Kubo M Singh S Khatri P Draghici S Bader GD Sander C Leonard WJ Pandey A Interleukin mediated signaling pathway PW:0000512 Pathway Ontology interleukin-7 signaling pathway PW:0000908 Pathway Ontology