IL-7 Signaling Pathway (Homo sapiens)

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IL-7 Signaling PathwayNFkBpathwayFYNPMAP2K1PBCL2L1PTK2BPCDKN1BSTAT5ACCND1PMAP2K2PMYCGSK3BSTAT5BPPIK3R2IL2RGMAPK3PJAK1PIL7STAT5AIL7RSTAT3BADPMAPK1PPAKT1PJAK3PIK3R1PIL2RASTAT5BNUCYSTAT1PProteinProteinmRNALigandReceptorProteinProtein - protein dissociationEnzyme ComplexSmall moleculeInduced activationInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationDeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageMolecule


Description

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 NetSlim database.

If you use this pathway, you must 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.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
89854view12:22, 6 October 2016MkutmonModified description
80223view17:41, 26 May 2015EgonwRestored the description with non-corrupted chars.
79472view12:07, 23 March 2015Zari
79279view22:36, 19 March 2015ZariAdded Identifier for STAT5A and STAT5B
78518view10:29, 7 January 2015MaintBotadded missing graphIds
70018view01:51, 12 July 2013AlexanderPicoModified title
67387view10:45, 26 June 2013Christine ChichesterOntology Term : 'interleukin-7 signaling pathway' added !
63214view20:59, 8 May 2013MaintBotUpdating gpml version
48440view14:42, 24 May 2012NetPathModified description
45369view21:00, 7 October 2011AlexanderPicoOntology Term : 'DOID:8406' removed !
45139view01:02, 7 October 2011AlexanderPicofixed db ref
44849view09:48, 6 October 2011MartijnVanIerselOntology Term : 'Interleukin mediated signaling pathway' added !
44628view18:11, 22 September 2011KhanspersUpdating content to NetSlim
44110view20:33, 24 August 2011KhanspersReverted to version '23:43, 1 March 2011' by Khanspers
44018view22:42, 22 August 2011Khanspers
44015view22:32, 22 August 2011KhanspersAdded category
44014view22:31, 22 August 2011KhanspersModified description
44013view22:28, 22 August 2011KhanspersUpdating pathway from NetSlim
41183view23:43, 1 March 2011MaintBotRemoved redundant pathway information and comments
35646view21:36, 12 February 2010KhanspersModified description
21111view11:30, 14 November 2008MaintBot[[Pathway:Homo sapiens:IL-7 NetPath 19]] moved to [[Pathway:WP205]]: Moved to stable identifier
8194view13:46, 7 January 2008MaintBot[[Pathway:Human:IL-7 NetPath 19]] moved to [[Pathway:Homo sapiens:IL-7 NetPath 19]]: Renaming species
7717view16:12, 18 December 2007MaintBotfixed category names
7256view12:41, 4 November 2007MaintBotAdded categories to GPML
6340view22:18, 22 May 2007A.Pandeygpml file for [[Human:IL-7_NetPath_19]]

External references

DataNodes

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NameTypeDatabase referenceComment
AKT1Protein207 (Entrez Gene)
BADProtein572 (Entrez Gene)
BCL2L1Rna598 (Entrez Gene)
CCND1Rna595 (Entrez Gene)
CDKN1BRna1027 (Entrez Gene)
FYNProtein2534 (Entrez Gene)
GSK3BProtein2932 (Entrez Gene)
IL2RARna3559 (Entrez Gene)
IL2RGProtein3561 (Entrez Gene)
IL7Protein3574 (Entrez Gene)
IL7RProtein3575 (Entrez Gene) 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.
JAK1Protein3716 (Entrez Gene) IL-7 stimulation induces tyrosine phosphorylation of the kinase JAK1 in human thymocytes
JAK3Protein3718 (Entrez Gene) IL7 stimulation induces increased phosphorylation of JAK3 in normal human chondrocytes and thymocytes.
MAP2K1Protein5604 (Entrez Gene)
MAP2K2Protein5605 (Entrez Gene)
MAPK1Protein5594 (Entrez Gene)
MAPK3Protein5595 (Entrez Gene)
MYCRna4609 (Entrez Gene)
PIK3R1Protein5295 (Entrez Gene)
PIK3R2Protein5296 (Entrez Gene)
PTK2BProtein2185 (Entrez Gene) IL-7 stimulation induces the phosphorylation of PTK2B in human chondrocytes.
STAT1Protein6772 (Entrez Gene) IL-7 stimulation leads to tyrosine phosphorylation of STAT1 in human CD4 T cells and murine YT-5 cells
STAT3Protein6774 (Entrez Gene) IL7 stimulation induces increased phosphorylation of STAT3 in normal human chondrocytes and T lymphoblasts.
STAT5AProtein6776 (Entrez Gene)
STAT5BProtein6777 (Entrez Gene)

Annotated Interactions

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